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Ambient Particulate Matter Exhibits Direct Inhibitory Effects on Oxidative Stress Enzymes
Abstract
A primary mechanistic hypothesis by which ambient air particles have a significant negative impact on human health is via the induction of pulmonary inflammatory responses mediated through the generation of reactive oxygen species (ROS). Development of a biosensor for the assessment of particulate ROS activity would be a significant advance in air pollution monitoring. The objective of this study was to evaluate whether air particulates interact directly with protective enzymes involved in oxidative stress responses. We performed enzyme activity assays on four enzymes involved in oxidative stress responses (Cu/Zn superoxide dismutase, Mn superoxide dismutase, glutathione peroxidase, and glutathione reductase) in the presence of particles of varying toxicities and found distinctive inhibition patterns. On the basis of these findings, we suggest a strategy for an enzyme bioassay that could be used to assess the potential of particles to generate ROS-induced responses.
... A remarkable increased SOD activity was found in subjects exposed to coal mining extraction after the antioxidant intervention compared to the lowered values found before such supplementation [4]. The decreased SOD activity found in the group of subjects living near the mines before the antioxidant intervention might be explained by the inhibition of heavy metals in important antioxidant enzymes [27,28]. The in vitro inhibition of GPx, SOD and GR activity was demonstrated by Hatzis and collaborators [27] after exposure to three different of PM (fly ashes from residual oil combustion, urban particulate matter and volcanic particulate ashes). ...
... The decreased SOD activity found in the group of subjects living near the mines before the antioxidant intervention might be explained by the inhibition of heavy metals in important antioxidant enzymes [27,28]. The in vitro inhibition of GPx, SOD and GR activity was demonstrated by Hatzis and collaborators [27] after exposure to three different of PM (fly ashes from residual oil combustion, urban particulate matter and volcanic particulate ashes). Before the antioxidant intervention GST activities increased in all groups when compared to controls [4]. ...
... Dust inhalation for long periods emitted by coal mining and coal burning lead to several lung pathologies, such as bronchitis, asthma, cancer, fibrosis, emphysema and pneumoconiosis, triggering a chronic inflammatory process, which is activated and linked to increased ROS generation and therefore systemic OS [18]. Moreover, several prospective studies have suggested that air pollution may be responsible for increased risk of developing lung cancer and cardiovascular diseases, among others, linking these risks with PM exposure and with ROS overgeneration [27,29,30]. ...
... Iron is a transition metal that catalyzes the production of hydroxyl radical (OH • ) by the Fenton reaction contributing to lipid peroxidation (Winterbourn, 1995;Aust et al., 2002). On the other hand, PM 10 directly interacts with antioxidant enzymes causing lost of enzymatic activity in a cell-free system (Hatzis et al., 2006) but remains unclear if the same effects will be observed in a cellular system and if ROS is directly involved in enzymatic activity loss. The aim of this study was to investigate the effect of PM 10 on oxidative stress markers and antioxidant enzymatic activity under sub-lethal conditions and search its relevance in the face of acute oxidative challenge in a human lung epithelial cell line. ...
... On the other hand, the OH • is generated by the soluble metals, but the insoluble particle fraction as OH • source also should be considered, since it has been demonstrated that insoluble fraction has OH • capacity formation (Knaapen et al., 2002). The oxidative effects observed in this study agree with previous reports (Ball et al., 2000;Fanizza et al., 2007;Hatzis et al., 2006;Jacobsen et al., 2008). For example, it has demonstrated that urban particulate matter from the National Institute of Standards and Technology (NIST) particles generated ROS in a cell-free assay (Ball et al., 2000) and in lung epithelial cells (Jacobsen et al., 2008). ...
... In addition, the LDH release was measured and less that 6% of death was found (Jacobsen et al., 2008). Later, it was demonstrated by Hatzis et al. (2006) that NIST particles in a range of 100-500 g/mL, were able to inhibit the activity of Mnand Cu/Zn-SOD. The NIST particles used in that study were also able to inhibit GR and GPx activities. ...
The aim of this study was to investigate the effect of airborne particulate matter with a mean aerodynamic diameter of < or =10microm (PM(10)) on oxidative stress markers and antioxidant enzymatic activity and its relevance in the face of acute oxidative challenge in a human lung epithelial cell line (A549). PM(10)-induced reactive oxygen species (ROS) generation and oxidative damage with no changes in cellular viability. In addition, PM(10) decreased glutathione (GSH) levels (54.9%) and the activity of the antioxidant enzymes superoxide dismutase (65%), catalase (31.2%), glutathione reductase (61.5%) and glutathione-S-transferase (42.39%). Trolox, a scavenger of reactive species, prevented the increase of ROS generation and the decrease in GSH levels but partially prevented PM(10)-induced oxidative damage. Interestingly, it was unable to avoid the decrease in the activity of antioxidant enzymes. Finally, the survival of the cells previously exposed to PM(10) and challenged with hydrogen peroxide was significantly lower. We conclude that the impairment in the antioxidant defense system induced by PM(10) weaken ROS detoxification which exacerbates cell death when these cells are exposed to an acute oxidative challenge.
... There is evidence that inhaled pollutant particles can interact with pneumonocytes after entering the lungs and may cause a chain of local and systemic inflammatory responses (Ghio et al., 2000;Pradhan et al., 2005). In addition, some studies have reported that elevated oxidative stress is involved in the adverse health effects of air pollution on the lungs (Kelly, 2003;Hatzis et al., 2006). Evidence from animal studies suggests that PM can consume and reduce antioxidants and related enzymes, produce free radicals, and then trigger oxidative stress, inflammation, and respiratory impairment (Hatzis et al., 2006). ...
... In addition, some studies have reported that elevated oxidative stress is involved in the adverse health effects of air pollution on the lungs (Kelly, 2003;Hatzis et al., 2006). Evidence from animal studies suggests that PM can consume and reduce antioxidants and related enzymes, produce free radicals, and then trigger oxidative stress, inflammation, and respiratory impairment (Hatzis et al., 2006). ...
Despite increasing concerns about the detrimental effects of air pollution on respiratory health, limited evidence is available on these effects in the Hong Kong population, especially in children. In this prospective cohort study between 2012 and 2017, we aimed to investigate the associations between exposure to air pollution (concen-trations of fine particulate matter [PM 2.5 ] and nitrogen dioxide [NO 2 ]) and respiratory health (lung function parameters and respiratory diseases and symptoms) in schoolchildren. We recruited 5612 schoolchildren aged 6-16 years in Hong Kong. We estimated the annual average concentrations of ambient PM 2.5 and NO 2 at each participant's address using spatiotemporal models. We conducted spirometry tests on all participants to measure their lung function parameters and used a self-administered questionnaire to collect information on their respiratory diseases and symptoms and a wide range of covariates. Linear mixed models were used to investigate the associations between exposure to air pollution and lung function. Mixed-effects logistic regression models with random effects were used to investigate the associations of exposure to air pollution with respiratory diseases and symptoms. In all of the participants, every 5-μg/m 3 increase in the ambient PM 2.5 concentration was associated with changes of − 13.90 ml (95 % confidence interval [CI]: − 23.65 ml, − 4.10 ml), − 4.20 ml (− 15.60 ml, 7.15 ml), 27.20 ml/s (− 3.95 ml/s, 58.35 ml/s), and − 19.80 ml/s (− 38.35 ml/s, − 1.25 ml/s) in forced expiratory volume in 1 s, forced vital capacity, peak expiratory flow, and maximal mid-expiratory flow, respectively. The corresponding lung function estimates for every 5-μg/m 3 increase in the ambient NO 2 concentration were − 2.70 ml (− 6.05 ml, 0.60 ml), − 1.40 ml (− 5.40 ml, 2.60 ml), − 6.60 ml/s (− 19.75 ml/s, 6.55 ml/s), and − 3.05 ml/s (− 11.10 ml/s, 5.00 ml/s), respectively. We did not observe significant associations between PM 2.5 /NO 2 exposure and most respiratory diseases and symptoms. Stratified analyses by sex and age showed that the associations between exposure to air pollution and lung function parameters were stronger in male participants and older participants (11-14 year old group) than in female participants and younger participants (6-10 year old group), respectively. Our results suggest that chronic exposure to air pollution is detrimental to the respiratory health of schoolchildren, especially that of older boys. Our findings reinforce the importance of air pollution mitigation to protect schoolchildren's respiratory health.
... Oxidative stress is caused by an imbalance between ROS production and anti-oxidant defenses (Pizzino et al., 2017). The detrimental effects of PM 10 on the anti-oxidant defense system (Hatzis et al., 2006) have also been well established (Chirino et al., 2010). Studies have shown that PM 10 lowered GSH levels in lung epithelial cells, which resulted in increased lipid peroxidation and protein oxidation (Chirino et al., 2010). ...
Purpose
In vivo data indicate that mouse corneas exposed to PM10 showed early perforation and thinning after infection with Pseudomonas aeruginosa. To understand the mechanisms underlying this finding, we tested the effects of PM10 and the mitochondria targeted anti-oxidant SKQ1 in immortalized human corneal epithelial cells (HCET) that were challenged with Pseudomonas aeruginosa strain 19660.
Methods
Mouse corneas were infected with strain 19660 after a 2 week whole-body exposure to PM10 or control air and assessed by clinical scores, slit lamp photography and western blot. HCET were exposed to 100μg/ml PM10 for 24h before challenge with strain 19660 (MOI 20). A subset of cells were pre-treated with 50nM SKQ1 for 1h before PM10 exposure. Phase contrast microscopy was used to study cell morphology, cell viability was measured by an MTT assay, and ROS by DCFH-DA. Levels of pro-inflammatory markers and anti-oxidant enzymes were evaluated by RT-PCR, western blot and ELISA. Reduced glutathione (GSH) and malondialdehyde (MDA) levels were evaluated by assay kits.
Results
In vivo, whole body exposure to PM10 vs. control air exposed mouse corneas showed early perforation and/or corneal thinning at 3 days post infection, accompanied by increased TNF-α and decreased SOD2 protein levels. In vitro, PM10 induced a dose dependent reduction in cell viability of HCET and significantly increased mRNA levels of pro-inflammatory molecules compared to control. Exposure to PM10 before bacterial challenge further amplified the reduction in cell viability and GSH levels. Furthermore, PM10 exposure also exacerbated the increase in MDA and ROS levels and phase contrast microscopy revealed more rounded cells after strain 19660 challenge. PM10 exposure also further increased the mRNA and protein levels of pro-inflammatory molecules, while anti-inflammatory IL-10 was decreased. SKQ1 reversed the rounded cell morphology observed by phase contrast microscopy, increased levels of MDA, ROS and pro-inflammatory molecules, and restored IL-10.
Conclusions
PM10 induces decreased cell viability, oxidative stress and inflammation in HCET and has an additive effect upon bacterial challenge. SKQ1 protects against oxidative stress and inflammation induced by PM10 after bacterial challenge by reversing these effects. The findings provide insight into mechanisms underlying early perforation and thinning observed in infected corneas of PM10 exposed mice.
... In the control group, the trend of changes in SOD3 levels was upward because it was an adaptive response of cells to acute exposure to an agent lasting less than 24 hours. (16) The SOD3 enzyme is an antioxidant that is widely available in the respiratory tract such as the lungs. (17) It was already well known that SOD3 is a major extracellular enzyme that plays an important role in reducing superoxide ions that have the potentials to cause oxidative damage. ...
Objective: To assess the effect of the Biosmart and safe concept on the levels of superoxide Dismutase 3 (SOD3) and reactive oxygen species (ROS) in the bus passenger nasal wash. Methods: This study is a non-blinding experimental design with a pretest-posttest measurement. The number of participants was 31 passengers of Biosmart and Safe Bus; divided into 2 groups: herbal masks and regular medical masks. Participants were divided into front, middle, and rear seat positions. Findings: The trend of SOD3 and ROS levels in the herbal mask group was increasing, while the trend in the medical mask group was decreasing. There was a significant difference in SOD3 levels in the middle seat position (p = 0.037) and ROS levels in the rear seat position (p = 0.022). There was a strong negative relationship between SOD3 levels and ROS levels in the herbal mask group (p = 0.016, r =-0.611). There was a significant difference in the levels of ROS on pretest-posttest of the medical mask group (p = 0.039), and the ROS levels in the herbal mask group approached a significant value (p = 0.059). There was no significant difference in SOD3 and ROS levels between the herbal mask and medical mask groups (p = 0.937; 0.810). Novelty : The ROS levels of Biosmart and Safe Bus passengers who use Herbal Masks are different from those using regular medical masks with lower levels. The SOD3 levels of Biosmart and Safe bus passengers who use herbal masks are different from those who use higher levels of regular medical masks.
... Another sign of a respiratory chain disorder is an increased production of ROIs, which may be associated with a decrease in the activity of antioxidant enzymes under the influence of APM: Cu/Zn superoxide dismutase, Mn superoxide dismutase, glutathione peroxidase, and glutathione reductase [37]. Under physiological conditions, the level of ROI formation ranges from low to moderate and plays a key role in routine cellular signaling. ...
The health risks associated with outdoor air pollution are of global concern. Atmospheric air pollution negatively affects a number of key aspects of human health, including the functioning of the respiratory, cardiovascular and central nervous systems, but many issues remain unresolved about the relationship between atmospheric air pollution and the development and course of pathologies. The review analyzes data from Russian and foreign sources on the effect of atmospheric particulate matter on the functional state of mitochondria. The effect of air pollution on structural changes in mitochondria, ATP synthesis, production of reactive oxygen species, damage to mitochondrial DNA, and mitochondrial membrane potential has been shown. The data presented in the review indicate the need for further studies of the functional state of mitochondria under the impact of solid particles in atmospheric air.
... Oxidative stress is thought to be an important underlying mechanism of action for the outcome of PM induces adverse health effects [11]. The mechanisms by which PM induces oxidative stress include the generation of Reactive Oxygen Species (ROS) and the inhibition of the intracellular enzymatic antioxidant defences [13]. When ROS levels exceed the cellular antioxidant capacity, a cascade of events is triggered in the cells, resulting in inflammation and significant cellular damage [14][15][16]. ...
Recent years have seen a significant increase in the scientific literature related to various methods for analyzing oxidative potential (OP) of atmospheric particulate matter (PM). The presence of several types of PM, differing chemical and physical properties, released by both anthropogenic and natural sources, leads to numerous health issues in living organisms and represents an attractive target for air quality monitoring. Therefore, several studies have focused on developing rapid and self-operative tests, employing different target molecules to assess OP of atmospheric aerosols as well as unique approaches to overcome some of the most common laboratory-related issues in this kind of analysis. This work provides an overview of online and automated systems, as well as a broad picture of the state-of-art of the various devices and methods developed on this topic over the last two decades. Moreover, representative studies on this subject will be discussed, analyzing the advantages and drawbacks of the developed automated techniques.
... 17,18 Although the biological pathways are not fully understood yet, evidence suggest that oxidative stress caused by PM is a key factor in understanding PM-associated health effects. [19][20][21][22] The ability of PM to generate reactive oxygen species (ROS) and thereby induce oxidative stress is measured by the oxidative potential (OP), an integrative metric of several physical and chemical properties of PM and its health effects. 23 Several recent studies have presented OP as a better predictor than concentration for assessing association with some cardiorespiratory diseases. ...
Background:
Fine particulate matter (PM2.5) has been found to be detrimental to respiratory health of children, but few studies have examined the effects of prenatal PM2.5 oxidative potential (OP) on lung function in infants and preschool children.
Objectives:
We estimated the associations of personal exposure to PM2.5 and OP during pregnancy on offspring objective lung function parameters and compared the strengths of associations between both exposure metrics.
Methods:
We used data from 356 mother-child pairs from the SEPAGES cohort. PM filters collected twice during a week were analyzed for OP, using the dithiothreitol (DTT) and the ascorbic acid (AA) assays, quantifying the exposure of each pregnant woman. Lung function was assessed with tidal breathing analysis (TBFVL) and nitrogen multiple-breath washout (N2MBW) test, performed at 6 wk, and airwave oscillometry (AOS) performed at 3 y. Associations of prenatal PM2.5 mass and OP with lung function parameters were estimated using multiple linear regressions.
Results:
In neonates, an interquartile (IQR) increase in OPvDTT (0.89 nmol/min/m3) was associated with a decrease in functional residual capacity (FRC) measured by N2MBW [β=-2.26mL; 95% confidence interval (CI): -4.68, 0.15]. Associations with PM2.5 showed similar patterns in comparison with OPvDTT but of smaller magnitude. Lung clearance index (LCI) and TBFVL parameters did not show any clear association with the exposures considered. At 3 y, increased frequency-dependent resistance of the lungs (Rrs7-19) from AOS tended to be associated with higher OPvDTT (β=0.09 hPa×s/L; 95% CI: -0.06, 0.24) and OPvAA (IQR=1.14 nmol/min/m3; β=0.12 hPa×s/L; 95% CI: -0.04, 0.27) but not with PM2.5 (IQR=6.9 μg/m3; β=0.02 hPa×s/L; 95% CI: -0.13, 0.16). Results for FRC and Rrs7-19 remained similar in OP models adjusted on PM2.5.
Discussion:
Prenatal exposure to OPvDTT was associated with several offspring lung function parameters over time, all related to lung volumes. https://doi.org/10.1289/EHP11155.
... In consistent with our results, it has been demonstrated that ambient PM induces oxidative stress and proinflammatory responses in human bronchial epithelial cells (31). Dusty PM was demonstrated to trigger ROS production and inhibited anti-oxidant enzymes, and has a significant negative effect on human health (32). ...
Background: T Exposure of normal subjects to dust storm (DS) with different doses of ambient air-born dusty particulate matter (PM) causes memory and locomotion impairment, anxiety and depression-like behaviors. This study was designed to investigate the effect of sub-chronic exposure to DS with inhalation of ambient PM in a designed special chamber on cognition, anxiety, depression, locomotion behaviors, brain tissue inflammatory cytokines and antioxidant indices in healthy adult rats.
Methods: Adult male Wistar rats (250-300 g) were divided randomly into the 4 groups: Sham (clean air, contains the least dusty PM < 150 μg/m3), DS1 (200-500 μg/m3 PM), DS2 (500-2000 μg/m3 PM) and DS3 (2000- 8000 μg/m3 PM). Rats were exposed to the clean air or different sizes and concentrations of PM in DS during the first 4 consecutive days of each week in an experimental actual-ambient dust exposure chamber.
Results: Sub-chronic exposing to dust storm PM impaired avoidance memory and locomotion, increased anxiety and depression like behaviors. These disturbances were in line with increased levels of inflammatory cytokines in brain tissue and suppressing the antioxidant indexes.
Conclusion: Current findings indicated that exposure to ambient PM due to DS caused cognitive, anxiety, depression-like and locomotion behaviors impairment by increasing the neuroinflammatory responses and suppressing the antioxidant indexes in the brain.
... The African continent is home to some of the highest ambient air pollution concentrations in the world, driven largely by rapid urbanization, incomplete vehicle and industry emissions regulations, and the use of biomass fuels [70,71]. Particulate matter causes both alveolar and systemic inflammation [72][73][74][75] that is associated with increased risk of both cardiovascular disease and acute coronary events [11,[76][77][78][79][80]. Using ambulatory air quality monitors, our group has demonstrated that personal air pollution exposure in southwestern Uganda is higher than international air quality standards and associated with respiratory morbidity [81]. ...
Background
Chronic obstructive pulmonary disease (COPD) is a leading cause of global mortality. In high-income settings, the presence of cardiovascular disease among people with COPD increases mortality and complicates longitudinal disease management. An estimated 26 million people are living with COPD in sub-Saharan Africa, where risk factors for co-occurring pulmonary and cardiovascular disease may differ from high-income settings but remain uncharacterized. As non-communicable diseases have become the leading cause of death in sub-Saharan Africa, defining multimorbidity in this setting is critical to inform the required scale-up of existing healthcare infrastructure.
Methods
We measured lung function and carotid intima media thickness (cIMT) among participants in the UGANDAC Study. Study participants were over 40 years old and equally divided into people living with HIV (PLWH) and an age- and sex-similar, HIV-uninfected control population. We fit multivariable linear regression models to characterize the relationship between lung function (forced expiratory volume in one second, FEV1) and pre-clinical atherosclerosis (cIMT), and evaluated for effect modification by age, sex, smoking history, HIV, and socioeconomic status.
Results
Of 265 participants, median age was 52 years, 125 (47%) were women, and 140 (53%) were PLWH. Most participants who met criteria for COPD were PLWH (13/17, 76%). Median cIMT was 0.67 mm (IQR: 0.60 to 0.74), which did not differ by HIV serostatus. In models adjusted for age, sex, socioeconomic status, smoking, and HIV, lower FEV1 was associated with increased cIMT (β = 0.006 per 200 mL FEV1 decrease; 95% CI 0.002 to 0.011, p = 0.01). There was no evidence that age, sex, HIV serostatus, smoking, or socioeconomic status modified the relationship between FEV1 and cIMT.
Conclusions
Impaired lung function was associated with increased cIMT, a measure of pre-clinical atherosclerosis, among adults with and without HIV in rural Uganda. Future work should explore how co-occurring lung and cardiovascular disease might share risk factors and contribute to health outcomes in sub-Saharan Africa.
... In the control group, the trend of changes in SOD3 levels was upward because it was an adaptive response of cells to acute exposure to an agent lasting less than 24 hours. (16) The SOD3 enzyme is an antioxidant that is widely available in the respiratory tract such as the lungs. (17) It was already well known that SOD3 is a major extracellular enzyme that plays an important role in reducing superoxide ions that have the potentials to cause oxidative damage. ...
Objective: To assess the effect of the Biosmart and safe concept on the levels
of superoxide Dismutase 3 (SOD3) and reactive oxygen species (ROS) in the
bus passenger nasal wash. Methods: This study is a non-blinding experimental
design with a pretest-posttest measurement. The number of participants was
31 passengers of Biosmart and Safe Bus; divided into 2 groups: herbal masks
and regular medical masks. Participants were divided into front, middle, and
rear seat positions. Findings: The trend of SOD3 and ROS levels in the herbal
mask group was increasing, while the trend in the medical mask group was
decreasing. There was a significant difference in SOD3 levels in the middle seat
position (p = 0.037) and ROS levels in the rear seat position (p = 0.022). There
was a strong negative relationship between SOD3 levels and ROS levels in the
herbal mask group (p = 0.016, r = -0.611). There was a significant difference in
the levels of ROS on pretest-posttest of the medical mask group (p = 0.039),
and the ROS levels in the herbal mask group approached a significant value (p
= 0.059). There was no significant difference in SOD3 and ROS levels between
the herbal mask and medical mask groups (p = 0.937; 0.810). Novelty : The ROS
levels of Biosmart and Safe Bus passengers who use Herbal Masks are different
from those using regular medical masks with lower levels. The SOD3 levels of
Biosmart and Safe bus passengers who use herbal masks are different from
those who use higher levels of regular medical masks.
Keywords: Biosmart and Safe Bus; herbal mask; nasal wash; ROS; SOD3
... They observed a decrease in state 3 respiratory rate in both subsarcolemmal mitochondria and interfibrillar mitochondria subpopulations. Another sign of an impaired respiratory chain is the overproduction of ROS that can be attributed to the downregulation of antioxidant enzymes or loss of their activity [89]. In a study examining the effects of air pollution on the white and brown adipose tissue in mice, it was demonstrated that superoxide production increased in the . ...
Environmental pollution is a major cause of global mortality and burden of disease. All chemical pollution forms together may be responsible for up to 12 million annual excess deaths as estimated by the Lancet Commission on pollution and health as well as the World Health Organization. Ambient air pollution by particulate matter (PM) and ozone was found to be associated with an all-cause mortality rate of up to 9 million in the year 2015, with the majority being of cerebro- and cardiovascular nature (e.g. stroke and ischemic heart disease). Recent evidence suggests that exposure to airborne particles and gases contributes to and accelerates neurodegenerative diseases. Especially, airborne toxic particles contribute to these adverse health effects. Whereas it is well established that air pollution in the form of PM may lead to dysregulation of neurohormonal stress pathways and may trigger inflammation as well as oxidative stress, leading to secondary damage of cardiovascular structures, the mechanistic impact of PM-induced mitochondrial damage and dysfunction is not well established. With the present review we will discuss similarities between mitochondrial damage and dysfunction observed in the development and progression of cardiovascular disease and neurodegeneration as well as those adverse mitochondrial pathomechanisms induced by airborne PM.
... Previous studies show that regular PA enhances the production of antiinflammatory markers and simultaneously constrains the production of inflammatory markers [43,44]. Conversely, PM 2.5 is associated with a higher level of inflammation and oxidative stress [45]. Clearly, higher levels of PA may increase the inhalation of particles, which will elevate pulmonary inflammation. ...
Background: Physical activity (PA) increases a person’s inhalation of air pollutants due to greater ventilation, possibly leading to larger adverse health effects. This study aims to investigate the combined effects of long-term exposure to fine particulate matter (PM2.5) and habitual PA on lung function in adults.
Methods: This was a longitudinal cohort study that included 278,065 Taiwan residents with an age of 20 years old or above who joined a standard medical screening programme between 2001 and 2014. Each participant received at least one medical examination (including spirometric, blood and urinary tests and a standard self-administered questionnaire survey) during the study period. We estimated the 2-year average PM2.5 concentrations at each participant’s address using a new physical model based on observational data. Information on the participants’ PA was collected using the standard self-administrated questionnaire. Generalised linear mixed models were used to investigate the combined effects of PM2.5 and PA on pulmonary function. We also performed stratified analyses by different levels of PM2.5 exposure and habitual PA.
Results: Each 10 MET-h increase in PA was associated with a higher level of 0.20%, 0.16%, and 0.19% in forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and maximum mid-expiratory flow (MMEF), respectively, after adjusting for PM2.5 exposure and a wide range of covariates including age, sex education, body mass index, lifestyles and health conditions. Each 10 μg/m3 increase in PM2.5 was associated with a lower FVC, FEV1 and MMEF (2.43%, 2.78% and 3.10%, respectively). Negative interactions were observed and PM2.5 exposure was associated with a greater reduction in lung function among the participants with higher PA levels.
Conclusions: We found significant negative interaction effects between long-term exposure to PM2.5 and habitual PA, suggesting that the increased intake of PM2.5 due to PA may attenuate the benefits of habitual PA on lung function. However, the PA benefits generally remained stable at different stratum of PM2.5 in the stratified analyses and habitual PA may still be recommended to people residing in relatively polluted regions.
... 5,6 Additionally, concurrent in vitro and in vivo experimentation has demonstrated the capacity of diesel exhaust particles (DEP) to stimulate xenobiotic and antioxidant defences, redox-sensitive signalling pathways, inflammatory cascades and the activation of airway nerve fibres. [7][8][9][10] In contrast, the toxic potential of non-tailpipe particulates, such as those produced by brake, tyre or clutch wear has received little attention. ...
Studies have emphasised the importance of combustion-derived particles in eliciting adverse health effects, especially those produced by diesel vehicles. In contrast, few investigations have explored the potential toxicity of particles derived from tyre and brake wear, despite their significant contributions to total roadside particulate mass. The objective of this study was to compare the relative toxicity of compositionally distinct brake abrasion dust (BAD) and diesel exhaust particles (DEP) in a cellular model that is relevant to human airways. Although BAD contained considerably more metals/metalloids than DEP (as determined by inductively coupled plasma mass spectrometry) similar toxicological profiles were observed in U937 monocyte-derived macrophages following 24 h exposures to 4–25 μg ml−1 doses of either particle type. Responses to the particles were characterised by dose-dependent decreases in mitochondrial depolarisation (p ≤ 0.001), increased secretion of IL-8, IL-10 and TNF-α (p ≤ 0.05 to p ≤ 0.001) and decreased phagocytosis of S. aureus (p ≤ 0.001). This phagocytic deficit recovered, and the inflammatory response resolved when challenged cells were incubated for a further 24 h in particle-free media. These responses were abrogated by metal chelation using desferroxamine. At minimally cytotoxic doses both DEP and BAD perturbed bacterial clearance and promoted inflammatory responses in U937 cells with similar potency. These data emphasise the requirement to consider contributions of abrasion particles to traffic-related clinical health effects.
... On the other hand, several lines of studies suggest that dusty PM inhibits directly the antioxidative enzymes by the generation of ROS. A primary mechanistic hypothesis by which ambient air dust particles have a significant negative impact on human health is via the generation of ROS [57]. Thus, our findings in the current study on oxidative stress in brain tissue due to dust storm exposure are in line with the results of other investigations on the negative effects of dusty PM on oxidative stress. ...
Objectives
Exposure of healthy subjects to ambient airborne dusty particulate matter (PM) causes brain dysfunction. This study aimed to investigate the effect of sub-chronic inhalation of ambient PM in a designed special chamber to create factual dust storm (DS) conditions on spatial cognition, hippocampal long-term potentiation (LTP), inflammatory cytokines, and oxidative stress in the brain tissue.
Methods
Adult male Wistar rats (250–300 g) were randomly divided into four groups: Sham (clean air, the concentration of dusty PM was <150 μg/m3), DS1 (200–500 μg/m3), DS2 (500–2000 μg/m3) and DS3 (2000–8000 μg/m3). Experimental rats were exposed to clean air or different sizes and concentrations of dust PM storm for four consecutive weeks (exposure was during 1–4, 8–11, 15–16 and 20–23 days, 30 min, twice daily) in a real-ambient dust exposure chamber. Subsequently, cognitive performance, hippocampal LTP, blood-brain barrier (BBB) permeability and brain edema of the animals evaluated. As well as, inflammatory cytokines and oxidative stress indexes in the brain tissue measured using ELISA assays.
Results
Exposing to dust PM impaired spatial memory (p < 0.001), hippocampal LTP (p < 0.001). These disturbances were in line with the severe damage to respiratory system followed by disruption of BBB integrity (p < 0.001), increased brain edema (p < 0.001), inflammatory cytokines (p < 0.001) excretion and oxidative stress (p < 0.001) in brain tissue.
Conclusions
Our study showed that exposure to ambient dust PM increased brain edema and BBB permeability, induced memory impairment and hippocampal LTP deficiency by increasing the inflammatory responses and oxidative stress in the brain of the rats.
... The biological mechanism underlying the associations between air pollution and lung function parameters is unclear. Previous studies have hypothesized the involvement of pulmonary inflammation (Ghio et al. 2000) or elevated oxidative stress (Hatzis et al. 2006). Animal studies have shown that PM 2:5 can induce oxidative stress, inflammation, and pulmonary impairment via the generation of free radicals and consumption of antioxidants and related enzymes (Riva et al. 2011). ...
Background:
The association between long-term exposure to ambient fine particulate matter with aerodynamic diameter
≤
2.5
μ
m
(
PM
2.5
) and lung function in young people remains uncertain, particularly in Asia, where air pollution is generally a serious problem.
Objectives:
This study investigated the association between long-term exposure to ambient
PM
2.5
and lung function in Taiwanese children, adolescents, and young adults.
Methods:
This study comprised 24,544 participants 6-24 years of age, with 33,506 medical observations made between 2000 and 2014. We used a spatiotemporal model to estimate
PM
2.5
concentrations at participants' addresses. Spirometry parameters, i.e., forced vital capacity (FVC), forced expiratory volume in 1 s (
FEV
1
), and maximum midexpiratory flow (MMEF), were determined. A generalized linear mixed model was used to examine the associations between long-term exposure to ambient
PM
2.5
and lung function. The odds ratios (ORs) of poor lung function were also calculated after adjusting for a range of covariates.
Results:
Every
10
-
μ
g
/
m
3
increase in the 2-y average
PM
2.5
concentration was associated with decreases of 2.22% [95% confidence interval (CI):
-
2.60
,
-
1.85
], 2.94 (95% CI:
-
3.36
,
-
2.51
), and 2.79% (95% CI:
-
3.15
,
-
2.41
) in the FVC,
FEV
1
, and MMEF, respectively. Furthermore, it was associated with a 20% increase in the prevalence of poor lung function (OR: 1.20; 95% CI: 1.12, 1.29).
Conclusions:
Two-year ambient
PM
2.5
concentrations were inversely associated with lung function and positively associated with the prevalence of poor lung function in children, adolescents, and young adults in Taiwan. https://doi.org/10.1289/EHP5220.
... 1,2 Indeed, epidemiologic studies have shown that chronic exposures to fine particulate matter (eg, particulate matter with an aerodynamic diameter < 2.5 mm [PM 2.5 ]) and ozone are associated with morbidity and mortality due to respiratory disease. [3][4][5][6][7] Long-term exposure to PM 2.5 has been shown to increase airway oxidative stress and inflammation in animal studies 8,9 and lung function decrements in human studies. 10 Exposure to ozone also causes oxidative stress from free radical formation, airway inflammation, and lung function decrements. ...
Background:
Chronic exposures to particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5) and ozone pollution can affect respiratory function. ARDS, an often lethal respiratory failure, is most common among older adults. However, few epidemiology studies have investigated an association between air pollution and the risk of ARDS.
Methods:
This observational study was conducted to estimate air pollution exposures at the ZIP code level and hospital admissions with ARDS among US Medicare beneficiaries aged ≥ 65 years from 2000 to 2012. A two-pollutant generalized linear mixed model, adjusting for sex, age, race, median household income, smoking, and weather, was applied.
Results:
There were a total of 1,164,784 hospital admissions with ARDS in the cohort. Increases of 1 µg/m3 in annual average PM2.5 and of 1 parts per billion in annual average ozone were associated with increases in annual hospital admission rates for ARDS of 0.72% (95% CI, 0.62-0.82) and 0.15% (95% CI, 0.08-0.22), respectively. In low-pollution regions (annual average PM2.5 level < 12 µg/m3 and annual average ozone level < 45 parts per billion), the same annual increase in PM2.5 and ozone were associated with increases in annual hospital admission rates for ARDS of 1.50% (95% CI, 1.27-1.72) and 0.27% (95% CI, 0.16-0.38).
Conclusions:
Long-term exposures to PM2.5 and ozone were associated with increased risk of ARDS among older adults in the United States, including exposures below current annual US National Ambient Air Quality Standards.
... 39 Evidence from experiments on mice also shows that exposure to ambient air particles could lead to pulmonary inflammation, resulting in anthracosis and emphysema. 40 Further studies are warranted to illustrate the mechanism. ...
Background/Aim: Previous studies have shown the short-term effects of fine particulate matter (PM2.5) on lung function. However, the effects of long-term exposure to PM2.5 on lung function and chronic obstructive pulmonary disease (COPD) are not well-documented. This study aimed to investigate the satellite-based estimates of long-term exposure to PM2.5 and its association with lung function and COPD in a large prospective Taiwan cohort.
Methods: A total of 366,756 participants aged 20 years or older were recruited with 1,031,849 spirometry tests in Taiwan in 2001-2014. We performed generalized linear mixed models to examine the associations between PM2.5 and lung function adjusting for a wide range of confounders. For the 125,475 participants who were free of COPD in baseline, we used cox proportional hazard regression models to investigate the PM2.5 effects on COPD development.
Results: PM2.5 was associated with lower lung function. After adjusting for confounders, participants with 4th quantile of PM2.5 had a decrease of 3.61% (95% confidence interval (CI): -3.76 to -3.47), 4.35% (95%CI: -4.36 to -4.34), and 7.75% (95%CI: -7.96 to -7.55) in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and maximum mid-expiratory flow (MMEF), respectively. They also had a faster decline of 0.24%, 0.64%, and 1.62% in FVC, FEV1, and MMEF, respectively. Compared to the participants with 1st quantile of PM2.5, participants with the 4th, 3rd and 2nd quantiles of PM2.5 had a hazard risk of 1.10 (1.00, 1.22), 1.15 (1.03, 1.27) and 1.24 (1.12, 1.37) in COPD development, respectively.
Conclusions: Long-term exposure to ambient PM2.5 is associated with decrease in pulmonary function and increased risk of COPD incident in Taiwan adults.
... 39 Evidence from experiments on mice also shows that exposure to ambient air particles could lead to pulmonary inflammation, resulting in anthracosis and emphysema. 40 Further studies are warranted to illustrate the mechanism. ...
Background: Information on the effects of long-term exposure to fine particulate matter with an aerodynamic diameter of 2·5 μm or less (PM2·5) on lung health is scarce. We aimed to investigate the associations between long-term exposure to PM2·5, lung function, and chronic obstructive pulmonary disease (COPD) in a large-scale longitudinal cohort.
Methods: We included 285 046 participants aged 20 years or older from the Taiwan MJ Health Management Institution cohort, who were recruited between 2001 and 2014 and had spirometric tests during the medical examination visit. We used a satellite-based spatiotemporal model to estimate the 2-year average ground concentration of PM2·5 (for the calendar year of each participant's medical examination and for the previous year) at each participant's address. We used the generalised linear mixed model to examine the associations between PM2·5 concentrations and lung function and the Cox proportional hazard regression model with time-dependent covariates to investigate the PM2·5 effects on COPD development.
Findings: Every 5 μg/m3 increment in PM2·5 was associated with a decrease of 1·18% for forced vital capacity (FVC), 1·46% for forced expiratory volume in 1 s (FEV1), 1·65% for maximum mid-expiratory flow (MMEF), and 0·21% for FEV1:FVC ratio. The decrease accelerated over time. Additional annual declines were observed for FVC (0·14%), FEV1 (0·24%), MMEF (0·44%), and FEV1:FVC ratio (0·09%). Compared with the participants exposed to the first quartile of PM2·5, participants exposed to the fourth, third, and second quartiles of PM2·5 had a hazard ratio of 1·23 (95% CI 1·09–1·39), 1·30 (1·16–1·46), and 1·39 (1·24–1·56) for COPD development, respectively.
Interpretation: Long-term exposure to ambient PM2·5 is associated with reduced, and faster declines in, lung function. Long-term exposure to ambient PM2·5 is also associated with an increased risk of the incidence of COPD. This study reinforces the urgency of global strategies to mitigate air pollution for improvement of pulmonary health and prevention of COPD.
Funding: Environmental Health Research Fund of the Chinese University of Hong Kong and PhD Studentship of the Chinese University of Hong Kong.
... The mechanism responsible for the effect of chronic exposure to air pollution on COPD in adults is unknown, but oxidative stress and pulmonary inflammation have been suggested to be main mechanisms in animal studies [37,38]. We found that NO2 and PM2.5 were associated with COPD prevalence. ...
This study was undertaken to investigate the associations between chronic exposure to particulate matter of medium aerodynamic diameter ≤10 or ≤2.5 µm (PM10 or PM2.5) and nitrogen dioxide (NO2) levels and lung function and to examine a possible change in these relationships by demographic and lifestyle factors. Chronic obstructive pulmonary disease (COPD) was defined using the Global Initiative for COPD criteria (forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) of <70%). Associations of lung function and COPD with PM10 or PM2.5 or NO2 were examined using linear and logistic regression analyses among 1264 Korean adults. The highest tertiles of PM2.5 (≥37.1 μg/m3) and NO2 (≥53.8 μg/m3) exposure were significantly associated with COPD (highest versus lowest tertile of PM2.5: adjusted odds ratio (OR) = 1.79, 95% CI: 1.02–3.13; highest versus lowest tertile of NO2: adjusted OR = 1.83, 95% CI: 1.04–3.21). A 10 μg/m3 increase in PM10 concentration was associated with a 1.85 L (95% CI –3.65 to –0.05) decrease in FEV1 and a 1.73 L (95% CI –3.35 to –0.12) decrease in FVC, with the strongest negative association among older people and those with less education. Reduced lung function was associated with PM2.5 exposure in subjects with no physical activity. This study provides evidence that exposure to ambient air pollution has adverse effects on lung function in adults.
... Experimental studies provide evidence that short-term exposure to NO 2 and particulate matter can induce endogenous release of ROS in exposed lung epithelial cells. This leads to allergic responses, pulmonary inflammation and pulmonary remodelling [32][33][34]. ...
Current evidence concerning the impact of exposure to traffic-related air pollution (TRAP) on adult respiratory morbidity mainly comes from cross-sectional studies. We sought to establish more robust measures of this association and potential gene–environment interactions using longitudinal data from an established cohort study.
Associations between measures of TRAP (nitrogen dioxide (NO 2 ) and distance to major roads) and wheeze, asthma prevalence and lung function were investigated in participants of the Tasmanian Longitudinal Health Study at 45- and 50-year follow-ups. Generalised estimating equations were used to quantify associations and the potential modifying effect of glutathione S -transferase gene variants.
Living <200 m from a major road was associated with increased prevalence of current asthma and wheeze, and lower lung function. The association between living <200 m from a major road and current asthma and wheeze was more marked for carriers of the GSTT1 null and GSTP1 val / val or ile / val genotypes. Over the 5-year period, higher NO 2 exposures were associated with increased current asthma prevalence. Higher NO 2 exposure was associated with lower forced vital capacity for carriers of the GSTT1 null genotype.
TRAP exposures were associated with increased risk of asthma, wheeze and lower lung function in middle-aged adults. The interaction with the GSTT1 genotype suggests that deficient antioxidant mechanisms may play a role in these adverse health effects.
... Secondary inorganic aerosols (nitrate,NO 3 − and sulfate, SO 4 2− ) have been recently associated with short-term effects on cardiovascular Ito et al., 2011) and respiratory health (Ostro et al., 2009;Atkinson et al., 2010;Kim et al., 2012;Son et al., 2012) hospital admissions. In addition, metals have been associated with different outcomes, for example: nickel with cardiovascular hospital admissions (Bell et al., 2009;Mostofsky et al., 2012) and cardiac function changes (Lippmann et al., 2006); zinc with oxidative stress and inflammation (Gilmour et al., 2006;Hatzis et al., 2006;Charrier and Anastasio, 2011), and; water soluble zinc and copper with cardiac oxidative stress (Gottipolu et al., 2008). ...
... -Ambient PM exhibits direct inhibitory effects on protective enzymes (such as copper/zinc superoxide dismutase (CuZnSOD), manganese superoxide dismutase (MnSOD), and glutathione peroxidase and reductase) involved in oxidative stress responses, which can lead to the accumulation of ROS [12]. ...
... Interestingly, there were increases in SOD activity in exposed cells 24 h after exposure, and decreases in SOD activity in exposed cells 48 h and 72 h after exposure, versus control cells. Another study using enzyme activity assays found acute inhibition of ambient PM on oxidative stress enzymes (including SOD and GPX) within 1 h after treatment (Hatzis et al., 2006). Therefore, exposure to PM may induce acute inhibition on activities of the antioxidant system by consuming existing antioxidant enzymes within a few hours, and then the inhibition may be attenuated by the body's adaptive responses to increase expression of antioxidant enzymes after exposure, which may be achieved by activating a rapid bone marrow response to PM exposure (Mukae et al., 2001) or prompt cellular signaling to increase gene expressions (Churg et al., 2005). ...
The association of systemic antioxidant activity with ambient air pollution has been unclear. A panel of 40 healthy college students underwent repeated blood collection for 12 occasions under three exposure scenarios before and after relocating from a suburban area to an urban area in Beijing, China in 2010-2011. We measured various air pollutants including fine particles (PM2.5) and determined circulating levels of antioxidant enzymes extracellular superoxide dismutase (EC-SOD) and glutathione peroxidase 1 (GPX1) in the laboratory. An interquartile range increase of 63.4 μg/m(3) at 3-d PM2.5 moving average was associated with a 6.3% (95% CI: 0.6, 12.4) increase in EC-SOD and a 5.5% (95% CI: 1.3, 9.8) increase in GPX1. Several PM2.5 chemical constituents, including negative ions (nitrate and chloride) and metals (e.g., iron and strontium), were consistently associated with increases in EC-SOD and GPX1. Our results support activation of circulating antioxidant enzymes following exposure to particulate air pollution.
Copyright © 2015 Elsevier Ltd. All rights reserved.
... The biologic mechanisms of air pollution toxicity on the adult lung are not well-studied in humans, because controlled human exposure studies do not lend themselves well to the study of longterm air pollution exposure. Animal studies suggest that long-term exposures result in pulmonary inflammation, oxidative stress, and pulmonary remodeling (37,38). A chamber study exposing mice prenatally and postnatally to filtered air versus concentrated ambient PM 2.5 at a level of 16.8 6 8.3 mg/m 3 found that the chronically exposed mice had reduced inspiratory and expiratory volumes at higher levels of transpulmonary pressure compared with unexposed mice (39). ...
Rationale:
Few studies have examined associations between long-term exposure to fine particulate matter (PM2.5) and lung function decline in adults.
Objectives:
To determine if exposure to traffic and PM2.5 is associated with longitudinal changes in lung function in a population-based cohort in the Northeastern United States, where pollution levels are relatively low.
Methods:
FEV1 and FVC were measured up to two times between 1995 and 2011 among 6,339 participants of the Framingham Offspring or Third Generation studies. We tested associations between residential proximity to a major roadway and PM2.5 exposure in 2001 (estimated by a land-use model using satellite measurements of aerosol optical thickness) and lung function. We examined differences in average lung function using mixed-effects models and differences in lung function decline using linear regression models. Current smokers were excluded. Models were adjusted for age, sex, height, weight, pack-years, socioeconomic status indicators, cohort, time, season, and weather.
Measurements and main results:
Living less than 100 m from a major roadway was associated with a 23.2 ml (95% confidence interval [CI], -44.4 to -1.9) lower FEV1 and a 5.0 ml/yr (95% CI, -9.0 to -0.9) faster decline in FEV1 compared with more than 400 m. Each 2 μg/m(3) increase in average of PM2.5 was associated with a 13.5 ml (95% CI, -26.6 to -0.3) lower FEV1 and a 2.1 ml/yr (95% CI, -4.1 to -0.2) faster decline in FEV1. There were similar associations with FVC. Associations with FEV1/FVC ratio were weak or absent.
Conclusions:
Long-term exposure to traffic and PM2.5, at relatively low levels, was associated with lower FEV1 and FVC and an accelerated rate of lung function decline.
... The biologic mechanisms of air pollution toxicity on the adult lung are not well-studied in humans, because controlled human exposure studies do not lend themselves well to the study of longterm air pollution exposure. Animal studies suggest that long-term exposures result in pulmonary inflammation, oxidative stress, and pulmonary remodeling (37,38). A chamber study exposing mice prenatally and postnatally to filtered air versus concentrated ambient PM 2.5 at a level of 16.8 6 8.3 mg/m 3 found that the chronically exposed mice had reduced inspiratory and expiratory volumes at higher levels of transpulmonary pressure compared with unexposed mice (39). ...
Rationale:
Limited prior data suggest an association between traffic-related air pollution and incident asthma in adults. No published studies assess the effect of long-term exposures to particulate matter less than 2.5 μm in diameter (PM2.5) on adult incident asthma.
Objectives:
To estimate the association between ambient air pollution exposures (PM2.5 and nitrogen dioxide, NO2) and development of asthma and incident respiratory symptoms.
Methods:
The Sister Study is a U.S. cohort study of risk factors for breast cancer and other health outcomes (n = 50,884) in sisters of women with breast cancer (enrollment, 2003-2009). Annual average (2006) ambient PM2.5 and NO2 concentrations were estimated at participants' addresses, using a national land-use/kriging model incorporating roadway information. Outcomes at follow-up (2008-2012) included incident self-reported wheeze, chronic cough, and doctor-diagnosed asthma in women without baseline symptoms.
Measurements and main results:
Adjusted analyses included 254 incident cases of asthma, 1,023 of wheeze, and 1,559 of chronic cough. For an interquartile range (IQR) difference (3.6 μg/m(3)) in estimated PM2.5 exposure, the adjusted odds ratio (aOR) was 1.20 (95% confidence interval [CI] = 0.99-1.46, P = 0.063) for incident asthma and 1.14 (95% CI = 1.04-1.26, P = 0.008) for incident wheeze. For NO2, there was evidence for an association with incident wheeze (aOR = 1.08, 95% CI = 1.00-1.17, P = 0.048 per IQR of 5.8 ppb). Neither pollutant was significantly associated with incident cough (PM2.5: aOR = 0.95, 95% CI = 0.88-1.03, P = 0.194; NO2: aOR = 1.00, 95% CI = 0.93-1.07, P = 0.939).
Conclusions:
Results suggest that PM2.5 exposure increases the risk of developing asthma and that PM2.5 and NO2 increase the risk of developing wheeze, the cardinal symptom of asthma, in adult women.
... Direct generation of ROS González-Flecha (2004) [63] N-acetylcysteine and deferoxamine Pinho et al. (2005) [64] Proinflammatory mediators released from PM-stimulated macrophages González-Flecha (2004) [63] Oxidative DNA damage González-Flecha (2004) [63] Aganasur et al. (2001) [65] Inhibitory effects on oxidative stress-related enzymes Hatzis et al. (2006) [66] Thiobarbituric acid reactive substances, protein carbonyls Possamai et al. (2010) [67] vitamins C and E Possamai et al. (2010) [67] Asbestos ROS formation (oxygen free radicals) Kamp et al. (1992) [68] Walker et al. (1992) [69] Green tea extract Luo et al. (1995) [70] Hydrogen peroxide, hydroxyl radical, and superoxide anion Lewczuk and Owczarek (1992) [71] SOD Fattman et al. (2006) [72] Activation of phagocytic cells Kamp et al. (1992) [68] Hei et al. (2006) [73] Walker et al. (1992) [69] Increased 8-isoprostane Pelclová et al. (2008) [74] 8-Hydroxy-2 í® í° -deoxyguanosine Marczynski et al. (2000) [75] As the diet is the main source of antioxidant micronutrients , a plausible link now exists between the exposure to air pollution and the quality of food consumed. ...
Overproduction of reactive oxygen and nitrogen species can result from exposure to environmental pollutants, such as ionising and nonionising radiation, ultraviolet radiation, elevated concentrations of ozone, nitrogen oxides, sulphur dioxide, cigarette smoke, asbestos, particulate matter, pesticides, dioxins and furans, polycyclic aromatic hydrocarbons, and many other compounds present in the environment. It appears that increased oxidative/nitrosative stress is often neglected mechanism by which environmental pollutants affect human health. Oxidation of and oxidative damage to cellular components and biomolecules have been suggested to be involved in the aetiology of several chronic diseases, including cancer, cardiovascular disease, cataracts, age-related macular degeneration, and aging. Several studies have demonstrated that the human body can alleviate oxidative stress using exogenous antioxidants. However, not all dietary antioxidant supplements display protective effects, for example,
β
-carotene for lung cancer prevention in smokers or tocopherols for photooxidative stress. In this review, we explore the increases in oxidative stress caused by exposure to environmental pollutants and the protective effects of antioxidants.
... Experimental studies have demonstrated that the mechanisms by which UAP inhalation promotes cardiorespiratory injuries might be related to important mechanistic differences. The interaction between pollutants and lung cells may activate pulmonary neural reflexes that initiates modifications in the autonomic nervous system (32) while concomitantly promoting inflammatory response (33) and oxidative stress (16,20). ...
This study examined
the hypothesis that acute exercise exposed to urban ambient particles
(UAP) inhalation could increase oxidative damage in the lung. Wistar
rats were submitted to UAP during a 20 or 60 min swimming exercise.
Longer periods of exercise (60 min exposure to UAP) showed higher
lipid peroxidation (MDA and Chemiluminescence) in the lung and
lower catalase activity. The findings indicate that the exposure of rats
to urban ambient particles during 60 min of swimming exercise results
in higher lipid peroxidation (MDA and Chemiluminesnce) and lower
CAT activity in the lungs. Short-term exposure to particulate matter
during exercise may be a biological risk, while longer periods of an
exercise session with exposure to particles can exacerbate oxidative
stress in the lungs
... Stress can be caused by self or others, work-related and/or personal, and short-term or continuous (Manning and Curtis, 2005). Although the literature on stress is vast, most researchers would take an interactive perspective, where stress is seen as a product of the relationship between a person and his/her environment, to study stress in the workplace (Caplan et al., 1975; Cooper and Payne, 1978; Greenhaus and Parasuranman, 1987; Cooper et al. 1988; Lazarus, 1991; Lu, 2005; Hatzis, 2006). According to Dr. Craig Hassed in his clinical reserach, there are three areas that affect workplace stress (Neiger, 2006), namely (i) the employee's perception of control, i.e. the ability to influence the work environment around them (Jackson, 1983), (ii) the ability to meet demands, i.e. by moderating expectations of employees (Jackson, 1983), and (iii) having appropriate support (Cummings, 1990). ...
... Interestingly, researchers have noted that pro-oxidants and electrophiles in the vapor phase of ambient air samples have an electrophile content approximately 10 times that found in the particle phase (Eiguren-Fernandez et al. 2010). Hatzis et al. (2006) evaluated the direct interaction of ambient particulates with protective enzymes present in oxidative stress responses. They found that copper/zinc (Cu/Zn) superoxide dismutase, manganese (Mn) superoxide dismutase, glutathione peroxidase, and glutathione reductase are consumed by interactions with particles of varying toxicities. ...
The US Environmental Protection Agency funded five academic research centers in 2005 to address uncertainties in the health effects caused by airborne particulate matter (PM) as suggested by the 1998 National Research Council report, “Research Priorities for Airborne Particulate Matter.” The centers employed multidisciplinary teams of epidemiologists, toxicologists, atmospheric scientists, engineers, and chemists to approach four key research themes: susceptibility to PM, biological mechanisms of PM response, exposure–response relationships, and source linkages. This review presents selected accomplishments in these categories from the past 5-year period. Publications from the centers are summarized to provide both an overview of the accomplishments to date and easy reference to much of the original literature published by the centers. Numerous investigators worked together within and across centers to investigate the relationships between atmospheric PM and health effects, including (a) the role of reactive oxygen species, inflammation, the nervous system, and the cardiovascular system, (b) particle characteristics such as size, composition, source, and temporal pattern of exposure, and (c) phenotypic and genotypic characteristics of the population that influence the level of exposure and risk in response to a given exposure.
... Covalent modification of biological molecules by reactive chemical compounds, particularly organics, and production of ROS are two key chemical mechanisms by which PM or its components can disrupt intracellular biochemistry, ultimately altering gene expression and subcellular organelle function in target cells. Center investigators demonstrated covalent binding of a cellular enzyme by electrophilic agents, including organic compounds, present in ambient PM (Rodriguez et al., 2005;Samet et al., 1999), and that particles can directly inhibit the activity of enzymes involved in oxidative stress response in a cell free assay (Hatzis et al., 2006). The PM Centers developed a large body of findings to support a growing literature on mechanisms related to oxidative stress and pro-inflammatory responses in cultured cells and laboratory animals. ...
... In vitro data has shown enzyme inactivation by pollutant components or ultrafine particles (Hatzis et al. 2006;Pigeolet et al. 1990). We recently conducted preliminary in vitro tests that showed pollutant-induced inactivation of the GPx-1 enzyme (Staimer et al. 2010). ...
Chemical components of air pollutant exposures that induce oxidative stress and subsequent inflammation may be partly responsible for associations of cardiovascular morbidity and mortality with airborne particulate matter and combustion-related pollutant gasses. However, epidemiologic evidence regarding this is limited. An exposure-assessment approach is to measure the oxidative potential of particle mixtures because it is likely that hundreds of correlated chemicals are involved in overall effects of air pollution on health. Oxidative potential likely depends on particle composition and size distribution, especially ultrafine particle concentration, and on transition metals and certain semivolatile and volatile organic chemicals. For health effects, measuring systemic oxidative stress in the blood is one feasible approach, but there is no universal biomarker of oxidative stress and there are many potential target molecules (lipids, proteins, DNA, nitric oxide, etc.), which may be more or less suitable for specific study goals. Concurrent with the measurement of oxidative stress, it is important to measure gene and/or protein expression of endogenous antioxidant enzymes because they can modify relations between oxidative stress biomarkers and air pollutants. Conversely, the expression and activities of these enzymes are modified by oxidative stress. This interplay will likely determine the observed effects of air pollutants on systemic inflammatory and thrombotic mediators and related clinical outcomes. Studies are needed to assess the reliability and validity of oxidative stress biomarkers, evaluate differences in associations between oxidative stress biomarkers and various pollutant measurements (mass, chemical components, and oxidative potential), and evaluate impacts of antioxidant responses on these relations.
... UFPs from traffic-related air pollution are enriched in organic redox-active compounds such as PAHs, quinones, and redox-active metals, which all induce oxidative stress [130,131]. Furthermore, particles can dissolve in alveolar fluid and diffuse directly into the blood [132], UFPs can enter cells freely [133] and cause further ROS production and antioxidant enzyme inactivation [59,134]. ROS leads to oxidative stress affecting lipids, proteins, and nucleic acids [135], and can consequently lead to airway and systemic inflammation. ...
Particulate matter (PM) air pollution has significant cardiopulmonary health effects. Serum biomarkers may elucidate the disease mechanisms involved and provide a means for biomonitoring exposed populations, thereby enabling accurate policy decisions on air quality standards to be made. For this review, research investigating association of blood serum biomarkers and exposure to PM was identified, finding 26 different biomarkers that were significantly associated with exposure. Recent evidence links different effects to different components of PM. Future research on biomarkers of effect will need to address exposure by all PM size fractions.
... This phenomenon may also be explained by epigenetic changes in the genes encoding GST and transcription factors, which could occur as the result of chronic inflammation and exposure to the genotoxic components of pollution, such as polycyclic aromatic hydrocarbons, aldehydes, black carbon and gases (Madrigano et al., 2011). Another possible hypothesis suggests a potential direct effect of some components of air pollution, especially ultrafine particles, which potentially cross the erythrocyte plasma membrane and exert a direct inhibitory effect on antioxidant enzymes, as postulated by Hatzis et al. (2006). This drop in erythrocyte antioxidant enzymes was also observed by Shinyashiki et al. (2008) in a study investigating elderly subjects exposed to traffic-related outdoor pollution. ...
Non-mechanised sugarcane harvesting preceded by burning exposes workers and the people of neighbouring towns to high concentrations of pollutants. This study was aimed to evaluate the respiratory symptoms, lung function and oxidative stress markers in sugarcane workers and the residents of Mendonça, an agricultural town in Brazil, during the non-harvesting and harvesting periods and to assess the population and individual exposures to fine particulate matter (PM(2.5)). Sugarcane workers and healthy volunteers were evaluated with two respiratory symptom questionnaires, spirometry, urinary 1-hydroxypyrene levels, and the measurement of antioxidant enzymes and plasma malonaldehyde during the non-harvesting and harvesting periods. The environmental assessment was determined from PM(2.5) concentration. PM(2.5) level increased from 8μg/m³ during the non-harvesting period to 23.5μg/m³ in the town and 61μg/m³ on the plantations during the harvesting period. Wheezing, coughing, sneezing, and breathlessness increased significantly in both groups during the harvesting period, but more markedly in workers. A decrease in lung function and antioxidant enzyme activity was observed in both populations during harvesting; this decrease was greater among the sugarcane workers. The urinary 1-hydroxypyrene levels only increased in the sugarcane workers during the harvesting period. The malonaldehyde levels were elevated in both groups, with a higher increase observed in the workers. This research demonstrates the exposure of sugarcane workers and the inhabitants of a neighbouring town to high PM(2.5) concentrations during the sugarcane harvest period. This exposure was higher among the sugarcane workers, as illustrated by both higher PM(2.5) concentrations in the sugarcane fields and higher urinary 1-hydroxypyrene levels in the volunteers in this group. The higher incidence of respiratory symptoms, greater decrease in lung function and more marked elevation of oxidative stress markers among the sugarcane workers during the harvest confirms the greater effect magnitude in this population and a dose-dependent relationship between pollution and the observed effects.
... 4,5,[7][8][9][10][11][12] In normal biological systems, generation of ROS as a result of natural aerobic metabolism is balanced by endogenous antioxidants. 13 When ROS levels exceed cellular antioxidant capacity, the redox status of the cell and its surrounding environment changes, thereby triggering a cascade of events associated with inflammation and, at higher concentrations, significant cellular damage. 14,15 Various approaches for measuring the oxidative activity of PM have been developed to study PM-induced oxidative stress. ...
Particulate matter (PM) air pollution has a significant impact on human morbidity and mortality; however, the mechanisms of PM-induced toxicity are poorly defined. A leading hypothesis states that airborne PM induces harm by generating reactive oxygen species in and around human tissues, leading to oxidative stress. We report here a system employing a microfluidic electrochemical sensor coupled directly to a particle-into-liquid sampler (PILS) system to measure aerosol oxidative activity in an on-line format. The oxidative activity measurement is based on the dithiothreitol (DTT) assay, where, after being oxidized by PM, the remaining reduced DTT is analyzed by the microfluidic sensor. The sensor consists of an array of working, reference, and auxiliary electrodes fabricated in a poly(dimethylsiloxane)-based microfluidic device. Cobalt(II) phthalocyanine-modified carbon paste was used as the working electrode material, allowing selective detection of reduced DTT. The electrochemical sensor was validated off-line against the traditional DTT assay using filter samples taken from urban environments and biomass burning events. After off-line characterization, the sensor was coupled to a PILS to enable on-line sampling/analysis of aerosol oxidative activity. Urban dust and industrial incinerator ash samples were aerosolized in an aerosol chamber and analyzed for their oxidative activity. The on-line sensor reported DTT consumption rates (oxidative activity) in good correlation with aerosol concentration (R(2) from 0.86 to 0.97) with a time resolution of approximately 3 min.
... In addition, there is a third SOD isoform located on the extracellular surface, EC-SOD. Glutathione peroxidase, an enzyme that catalyzes the reduction of hydroperoxides including hydrogen peroxide using glutathione as reducing substrate and glutathione reductase, a flavoprotein containing redox active disulfide bonds that catalyzes NADPHdependent reduction of oxidized glutathione and therefore is essential for maintaining levels of reduced glutathione in the cell [Hatzis et al., 2006]. Glutathione (GSH) and the oxidized form gluthatione disulfide (GSSG) are major antioxidants. ...
... This could occur through oxidative modification of amino acids or irreversible modification of enzyme function by electrophiles (Shinyashiki et al. 2008). In vitro data using enzyme suspensions have shown marked reduction in the activity of GPx-1, Cu,Zn-SOD, and/or manganese SOD from variety of particle surrogates (Hatzis et al. 2006). GPx-1 and Cu,Zn-SOD activities decreased in the lungs of rats following intratracheal instillation of diesel exhaust particles (Sagai et al. 1993). ...
Biomarkers of systemic inflammation have been associated with risk of cardiovascular morbidity and mortality.
We aimed to clarify associations of particulate matter (PM) air pollution with systemic inflammation using models based on size-fractionated PM mass and markers of primary and secondary aerosols.
We followed a panel of 29 nonsmoking elderly subjects with a history of coronary artery disease (CAD) living in retirement communities in the Los Angeles, California, air basin. Blood plasma biomarkers were measured weekly over 12 weeks and included C-reactive protein (CRP), fibrinogen, tumor necrosis factor-alpha (TNF-alpha) and its soluble receptor-II (sTNF-RII), interleukin-6 (IL-6) and its soluble receptor (IL-6sR), fibrin D-dimer, soluble platelet selectin (sP-selectin), soluble vascular cell adhesion molecule-1 (sVCAM-1), intracellular adhesion molecule-1 (sICAM-1), and myeloperoxidase (MPO). To assess changes in antioxidant capacity, we assayed erythrocyte lysates for glutathione peroxidase-1 (GPx-1) and copper-zinc superoxide dismutase (Cu,Zn-SOD) activities. We measured indoor and outdoor home daily size-fractionated PM mass, and hourly pollutant gases, total particle number (PN), fine PM elemental carbon (EC) and organic carbon (OC), estimated secondary organic aerosol (SOA) and primary OC (OCpri) from total OC, and black carbon (BC). We analyzed data with mixed models controlling for temperature and excluding weeks with infections.
We found significant positive associations for CRP, IL-6, sTNF-RII, and sP-selectin with outdoor and/or indoor concentrations of quasi-ultrafine PM < or = 0.25 microm in diameter, EC, OCpri, BC, PN, carbon monoxide, and nitrogen dioxide from the current-day and multiday averages. We found consistent positive but largely nonsignificant coefficients for TNF-alpha, sVCAM-1, and sICAM-1, but not fibrinogen, IL-6sR, or D-dimer. We found inverse associations for erythrocyte Cu,Zn-SOD with these pollutants and other PM size fractions (0.25-2.5 and 2.5-10 microm). Inverse associations of GPx-1 and MPO with pollutants were largely nonsignificant. Indoor associations were often stronger for estimated indoor EC, OCpri, and PN of outdoor origin than for uncharacterized indoor measurements. There was no evidence for positive associations with SOA.
Results suggest that traffic emission sources of OCpri and quasi-ultrafine particles lead to increased systemic inflammation and platelet activation and decreased antioxidant enzyme activity in elderly people with CAD.
... An opposite response was found by Howard and collaborators (1998) after antioxidant supplementation in subjects exposed by environmental tobacco smoke. As already mentioned, exposure to PM and heavy metals induces oxidative stress by inhibition of important antioxidant enzymes (Hatzis et al. 2006; Wang and Fowler 2008), an effect that may explain the decreased SOD activities found in the group of residents near the mining areas and also in the group directly exposed to SRHS incineration, as well as the decreased GPx activity found in the group of residents and workers of SRHS incineration and in the group of underground mine workers (Tables 5 and 6). Before the antioxidant intervention GST activities increased in all groups when compared to controls (Tables 5 and 6). ...
Coal mining and incineration of solid residues of health services (SRHS) generate several contaminants that are delivered into the environment, such as heavy metals and dioxins. These xenobiotics can lead to oxidative stress overgeneration in organisms and cause different kinds of pathologies, including cancer. In the present study the concentrations of heavy metals such as lead, copper, iron, manganese and zinc in the urine, as well as several enzymatic and non-enzymatic biomarkers of oxidative stress in the blood (contents of lipoperoxidation = TBARS, protein carbonyls = PC, protein thiols = PT, α-tocopherol = AT, reduced glutathione = GSH, and the activities of glutathione S-transferase = GST, glutathione reductase = GR, glutathione peroxidase = GPx, catalase = CAT and superoxide dismutase = SOD), in the blood of six different groups (n = 20 each) of subjects exposed to airborne contamination related to coal mining as well as incineration of solid residues of health services (SRHS) after vitamin E (800 mg/day) and vitamin C (500 mg/day) supplementation during 6 months, which were compared to the situation before the antioxidant intervention (Ávila et al., Ecotoxicology 18:1150-1157, 2009; Possamai et al., Ecotoxicology 18:1158-1164, 2009). Except for the decreased manganese contents, heavy metal concentrations were elevated in all groups exposed to both sources of airborne contamination when compared to controls. TBARS and PC concentrations, which were elevated before the antioxidant intervention decreased after the antioxidant supplementation. Similarly, the contents of PC, AT and GSH, which were decreased before the antioxidant intervention, reached values near those found in controls, GPx activity was reestablished in underground miners, and SOD, CAT and GST activities were reestablished in all groups. The results showed that the oxidative stress condition detected previously to the antioxidant supplementation in both directly and indirectly subjects exposed to the airborne contamination from coal dusts and SRHS incineration, was attenuated after the antioxidant intervention.
Growing trend of air pollution has become one of the familiar environmental hazards for the society. It is a mixture of toxic compounds emerging from both natural and anthropogenic sources. Depending on the source and rate of emission the components of air pollution change dramatically. The primary human-made sources of air pollution may include vehicle emissions, natural gas to heat homes, fuel oils, and by-products of manufacturing and power generation and fumes from chemical production. In addition to that, various hazardous substances such as methane and other gases are released by decomposing organic matter in soils, and other gases include ash and smoke from volcanic eruptions, which are frequently caused by humans. Various reports around the world have consistently demonstrated that air pollution is a significant adaptable risk factor for enhanced mortality. Air pollutants can harm the health of humans, animals, plants, and buildings. The pollutants are in the form of gases, solid particles, or liquid droplets. Ozone (O3), nitric oxide (NO), carbon monoxide (CO), nitrogen dioxide (NO2), and sulphur dioxide (SO2) are some of the gaseous pollutants that contribute to air pollution. The pollution is now the leading environmental cause of premature death. Cardiovascular events such as acute ischemic account for the majority of the additional mortality caused by air pollution. Aside from increased mortality, air contamination is linked to significant reductions in worker productivity. Exposure to air pollution has a wide range of negative consequences on people’s health. The effects of air pollution can be divided into short-term and long-term effects. The discomfort, such as irritation to the nose, eyes, throat or skin, as well as infections like bronchitis are short-term symptoms that are transient. It can also cause headaches, nausea and dizziness. The long-term effects of pollution can last for years and cause various respiratory diseases. Long-term damage to people’s nerves, brains, kidneys, liver, and other organs, birth defects are the consequences of air pollution (Brook et al. 2004; Newby et al. 2015; Zivin and Neidell 2018; Hamanaka and Mutlu 2018).
Objectives
The textile industry including readymade garment manufacturing contributes substantially to the foreign exchange earned by India. More than 45 million people are employed in this industry. Our previous study revealed a compromised lung function (obstructive and mixed) in readymade garment manufacturing workers in the Garden Reach-Metiabruz region of Kolkata. The present study was undertaken to evaluate the impact of the work environment on the immune health at the local and systemic levels of the workers of this region. Oxidative stress encountered by the workers was also assessed.
Materials and Methods
Male workers of age group 18–35 years ( n = 80) from readymade garment manufacturing units of Garden Reach-Metiabruz region of Kolkata, India were selected for the study. The control group was selected from the same region unexposed to the factory environment. Blood samples were collected from both groups for estimation of cytokines, C-reactive protein (CRP), cortisol and anti-oxidants of the subjects. Sputum samples from dust-exposed workers were studied for alveolar macrophages.
Results
Accumulation of alveolar macrophages in the sputum was noted in the workers which indicated a local inflammation. A systemic inflammatory state was revealed by elevated proinflammatory cytokines and CRP. Reduction in antioxidants noted is an indicator of oxidative stress in the workers.
Conclusion
A chronic proinflammatory condition exists in these workers and may be the underlying cause of the compromised respiratory status noted in the workers of this region. The inflammatory condition may lead to the pathogenesis of cardiovascular disorders, autoimmune disorders, etc., later in life. This might also influence the outcome of various respiratory infections like the current COVID-19.
There have been many studies on the relationship between fine particulate matter (PM2.5) and lung function. However, the impact of short-term or long-term PM2.5 exposures on lung function in children is still inconsistent globally, and the reasons for the inconsistency of the research results are not clear. Therefore, we searched the PubMed, Embase and Web of Science databases up to May 2022, and a total of 653 studies about PM2.5 exposures on children's lung function were identified. Random effects meta-analysis was used to estimate the combined effects of the 25 articles included. PM2.5 concentrations in short-term exposure studies mainly come from individual and site monitoring. And for every 10 μg/m³ increase, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1) and peak expiratory flow (PEF) decreased by 21.39 ml (95% CI: 13.81, 28.92), 25.66 ml (95% CI: 14.85, 36.48) and 1.76 L/min (95% CI: 1.04, 2.49), respectively. The effect of PM2.5 on lung function has a lag effect. For every 10 μg/m³ increase in the 1-day moving average PM2.5 concentration, FEV1, FVC and PEF decreased by 14.81 ml, 15.40 ml and 1.18 L/min, respectively. PM2.5 concentrations in long-term exposure studies mainly obtained via ground monitoring stations. And for every 10 μg/m³ increase, FEV1, FVC and PEF decreased by 61.00 ml (95% CI: 25.80, 96.21), 54.47 ml (95% CI: 7.29, 101.64) and 10.02 L/min (95% CI: 7.07, 12.98), respectively. The sex, BMI, relative humidity (RH), temperature (Temp) and the average PM2.5 exposure level modify the relationship between short-term PM2.5 exposure and lung function. Our study provides further scientific evidence for the deleterious effects of PM2.5 exposures on children's lung function, suggesting that exposure to PM2.5 is detrimental to children's respiratory health. Appropriate protective measures should be taken to reduce the adverse impact of air pollution on children's health.
Although carbon black (CB) particles have potential hazards to human health, the toxicological studies on CB are still limited. The purpose of this study was to investigate the effect of oxidative stress induced by ultrafine CB particles on apoptosis in vivo and vitro. Male C57BL/6 mice were inhalation exposed to CB for 28 days, and 16HBE cells were treated by CB particles and also added antioxidant (NAC). Antioxidant enzymes activities (CAT, SOD, GSH-Px) and ROS in the lungs and cells were evaluated. Apoptosis-related proteins (Bcl-2, Bax, Cleaved Caspase-3, pro-Caspase-3, Caspase-7, Caspase-8, Caspase-9, PARP-1) were tested by Western blot (WB), immunohistochemistry (IHC), and real-time PCR. The reduction of antioxidant enzymes activities and the addition of ROS in CB exposure groups were observed, and the gene and apoptosis-related proteins levels were increased in CB exposure mice. The results of CB-treated 16HBE cells were consistent with those of mice, and apoptosis rate was increased in CB-treated 16HBE cells. When the cells were treated with NAC, ROS induced by CB decreased, SOD and CAT activities of CB-treated 16HBE cells were increased. Apoptosis rate of 16HBE cells treated with NAC and CB was significantly decreased, and the expression of C-Caspase-3 was also decreased. Therefore, oxidative stress induced by ultrafine CB particles can elicit apoptosis in vivo and vitro. Antioxidants can significantly reduce oxidative damage and apoptosis induced by CB.
To clarify the effects of lung function following exposure to diesel engine exhaust (DEE) , we recruited 137 diesel engine testing workers exposed to DEE and 127 non-DEE-exposed workers as study subjects. We performed lung function tests and measured cytokinesis-block micronucleus (CBMN) cytome index and levels of urinary polycyclic aromatic hydrocarbons (PAHs) metabolites. There was a significant decrease of forced expiratory volume in 1 second (FEV1), ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/ FVC), maximal mid expiratory flow curve (MMF), forced expiratory flow at 50% of FVC (FEF50%), and forced expiratory flow at 75% of FVC (FEF75%) in the DEE-exposed workers than non-DEE-exposed workers (all p<0.05). Among all study subjects, the decreases of FEF75% were associated with the increasing levels of PAH metabolites (p<0.05), and there were negative correlations between FEV1, FEV1/FVC, MMF, FEF50%, and FEF75% with CBMN cytome index (all p<0.05). Our results show that long-term exposure to DEE can induce lung function decline which shows mainly obstructive changes and influence of small airways function. The decreased lung function is associated with internal dosage of DEE exposure, and accompany with the increasing CBMN cytome index.
Surface oxidation states of ultrafine particulate matter can influence the proinflammatory responses and reactive oxygen species levels in tissue. Surface active species of vehicle-emission soot can serve as electron transfer-mediators in mitochondrion. Revealing the role of surface oxidation state in particles-proteins interaction will promote the understanding on metabolism and toxicity. Here, the surface oxidation state was modeled by nitro/amino ligands on nanoparticles, the interaction with blood proteins were evaluated by capillary electrophoresis quantitatively. The nitro shown larger affinity than amino. On the other hand, the affinity to hemoglobin is 103 times larger than that to BSA. Further, molecular docking indicated the difference of binding intensity were mainly determined by hydrophobic forces and hydrogen bonds. These will deepen the quantitative understanding of protein-nanoparticles interaction from the perspective of surface chemical state.
Air quality in street canyons is of major importance, since the highest pollution levels are often encountered in these microenvironments. The canyon effect (reduced natural ventilation) makes them "hot spots" for particulate pollution contributing to adverse health effects for the exposed population. In this study we tried to characterize the influence of UFP (ultrafine particle) emissions from traffic on population exposure in an urban street canyon, by applying the intake fraction (iF) approach. One month long measurements of UFP levels have been monitored and used for the need of this study. We applied a three dimensional computational fluid dynamic (CFD) model based on real measurements for the simulation of UFP levels. We used infiltration factors, evaluated on a daily basis for the under study area, to estimate the indoor UFP levels. As a result the intake fraction for the pedestrians, residents and office workers is in the range of (1E-5)-(1E-4). The street canyon is mostly residential justifying partially the higher value of intake fraction for residents (1E-4). The above iF value is on the same order of magnitude with the corresponding one evaluated in a relative street canyon study. The total iF value in this microenvironment is one order of magnitude higher than ours, explained partially by the different use and activities. Two specific applications of iF to assess prioritization among emission sources and environmental justice issues are also examined. We ran a scenario with diesel and gasoline cars and diesel fueled vehicle seems to be a target source to improve overall iF. Our application focus on a small residential area, typical of urban central Athens, in order to evaluate high resolution iF. The significance of source-exposure relationship study in a micro scale is emphasized by recent research.
Copyright © 2015 Elsevier B.V. All rights reserved.
Recently, a branch of particulate matter research concerns on ultrafine particles found in the urban environment, which originate, to a significant extent, from traffic sources. In urban street canyons, dispersion of ultrafine particles affects pedestrian's short term exposure and resident's long term exposure as well. The aim of the present work is the development and the evaluation of a composite lattice Boltzmann model to study the dispersion of ultrafine particles, in urban street canyon microenvironment. The proposed model has the potential to penetrate into the physics of this complex system. In order to evaluate the model performance against suitable experimental data, ultrafine particles levels have been monitored on an hourly basis for a period of 35days, in a street canyon, in Athens area. The results of the comparative analysis are quite satisfactory. Furthermore, our modeled results are in a good agreement with the results of other computational and experimental studies. This work is a first attempt to study the dispersion of an air pollutant by application of the lattice Boltzmann method.
This document summarizes additional mechanistic information obtained in the first 6 years of the PM Centers' research since their establishment in 1999. Research performed as part of the EPA- funded Particle Centers has increased the understanding of the mechanisms of PM health effects. Progress has been made in understanding the dosimetry and distribution of particles throughout the body, pulmonary inflammation and vascular effects, asthma and allergen responses, cardiac effects, vascular and systemic inflammatory effects, and possible impact on the central nervous system. These findings have increased our understanding of the mechanisms of injury at the organ, tissue, cellular, and subcellular levels, and have begun to shed light on systemic interactions in the whole organism that contribute to adverse health outcomes.
The objective of this study was to compare the toxicological effects of different source-related ambient PM10 samples in regard to their chemical composition. In this context we investigated airborne PM from different sites in Aachen, Germany. For the toxicological investigation human alveolar epithelial cells (A549) and murine macrophages (RAW264.7) were exposed from 0 to 96 h to increasing PM concentrations (0-100 μg/ml) followed by analyses of cell viability, pro-inflammatory and oxidative stress responses. The chemical analysis of these particles indicated the presence of 21 elements, water-soluble ions and PAHs. The toxicological investigations of the PM10 samples demonstrated a concentration- and time-dependent decrease in cell viability and an increase in pro-inflammatory and oxidative stress markers.
In this study, we tested the influence of ambient air pollution on different phases of development of adult mice. With respect to adult weight, the animals that had spent their in utero period exposed to pollution showed less weight gain over their lifetime, as well as lower activity levels of the antioxidant enzymes catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx). Our study suggests that contact with atmospheric pollutants during the foetal period produces important changes on enzymatic erythrocyte antioxidant defense and weight in adult mice.
In the process of energy generation, particulate matter (PM) emissions derived from coal combustion expose humans to serious occupational diseases, which are associated with overgeneration of reactive oxygen species (ROS). The purpose of the present study is to better understand the relations between PM exposure derived from a coal electric-power plant and the oxidative damage in subjects (n=20 each group) directly (working at the burning area) or indirectly (working at the office or living in the vicinity of the electric-power plant=group of residents) exposed to airborne contamination, before and after daily supplementation with vitamins C (500mg) and E (800mg) during six months, which were compared to non-exposed subjects (control group). Several biomarkers of oxidative stress were examined such as levels of thiobarbituric acid reactive substances (TBARS), protein carbonyls (PC), protein thiols (PT) and vitamin E in plasma, levels of reduced glutathione (GSH) in whole blood, and of activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S-transferase (GST) in red cells. Before supplementation, TBARS and PC levels were significantly increased, levels of GSH and vitamin E were decreased, while the activities of SOD and CAT were increased in workers groups and GST were increased in all groups in compared to controls. After the antioxidant supplementation essentially all these biomarkers were normalized to control levels. The antioxidant intervention was able to confer a protective effect of vitamins C and E against the oxidative insult associated with airborne contamination derived from coal burning of an electric-power plant.
1. An ATP-dependent oxidation of cytochrome b was observed in submitochondrial particles from beef heart in the presence of succinate, malonate, sulfide, and antimycin A. The reaction was inhibited by rotenone, rutamycin, and uncoupling agents. Under the same conditions an ATP-dependent H2O2 production took place.
2. Spectrophotometric measurements also revealed an ATP-dependent reduction of flavin. In contrast to the oxidation of cytochrome b, the reduction of flavin required addition of catalytic amounts of NAD to the depleted submitochondrial particles.
3. An ATP-dependent, rotenone-sensitive, reduction of ferricyanide by succinate was observed which did not require the addition of NAD.
4. It was concluded that in beef heart submitochondrial particles the reversed electron transfer from cytochrome b driven by ATP takes place via a slowly autoxidizable electron carrier. In the absence of NAD, ferricyanide or oxygen can accept electrons from this carrier, and in the presence of NAD, the electrons can be channeled to a flavoprotein and to NAD.
5. These findings strongly suggest that in the reversal of electron transfer the energy coupling site is located between cytochrome b and the flavin of NADH dehydrogenase.
Urban particles have a complex heterogeneous composition. To determine which components contribute to the toxicity of inhaled ambient air particles, six different experiments were done using normal Sprague-Dawley rats exposed for 3 consecutive days, for 5 h per day, to either concentrated air particles (CAPs) or filtered air sham conditions (8–12 animals per experimental group per experiment). For each exposure, mass, sulfate, elemental carbon, organic carbon and elemental analysis by X-ray fluorescence were determined. Rotating factor analysis was used to identify component representatives for constituents with the same day-to-day variation. Bronchoalveolar lavage (BAL) was done 24 h after the last exposure on at least six randomly selected animals per group, assessing both cell and fluid parameters. RNA was collected from the lung tissue and BAL cells of each animal, then purified, pooled and hybridized to Affymetrix® rat genome expression microarrays to assess differences in mRNA between the CAPs and sham groups. Significant increases in neutrophils in BAL correlated with measured mass concentrations and particle components associated with urban traffic. Pro-inflammatory mediators/receptors, vascular activation mediators and organic chemical detoxification enzymes all indicated substantial increases in mRNA in CAPs-exposed compared with shamexposed animals. The mRNA detected for immune enhancers and vascular dilatation mediators were substantially decreased with CAPs exposure. Identifying cellular responses and mediators in relation to responsible components in the particles are important steps in understanding the effects of inhaled ambient particles.
Particulate air pollution has been shown to cause adverse health effects, and the ultrafine particle component has been implicated. The aim of the present study was to investigate whether an ultrafine particle exerted its effects through transition metals or other soluble factors released from the surface of the particles.
Both in vitro and in vivo models were used to test the imflammogenicity of carbon black (CB) and ultrafine carbon black (UfCB) and the role of transition metals was investigated by treating the particles with desferrioxamine mesylate (desferal), a transition metal chelator. Rats were instilled with particles and the cell population assessed by bronchoalveolar lavage (BAL). Calcium homeostasis in macrophages was assessed with a fluorimetric technique.
UfCB was inflammogenic compared with CB when instilled into Wistar rat lungs, an effect which could not be ameliorated by desferal treatment of the particles. Particle leachates produced no significant inflammation in vivo. In vitro experiments showed that the cytosolic calcium ion concentration in Mono Mac 6 cells was increased significantly after UfCB treatment and treatment of particles with desferal did not alter these effects. Particle leachates had no effect on cytosolic calcium ion concentration. Iron was not detected in leachates of the particles with the desferal assay, however, ng/mg of particles were detectable in citrate leachates with inductively coupled plasma-mass spectrometry (ICP-MS).
The increased inflammogenicity of UfCB compared with CB cannot be explained by soluble transition metals released from or by accumulation of iron at the particle surface. Differences may be accounted for by increased surface area or particle number.
Associations have been found between day-to-day particulate air pollution and increased risk of various adverse health outcomes, including cardiopulmonary mortality. However, studies of health effects of long-term particulate air pollution have been less conclusive.
To assess the relationship between long-term exposure to fine particulate air pollution and all-cause, lung cancer, and cardiopulmonary mortality.
Vital status and cause of death data were collected by the American Cancer Society as part of the Cancer Prevention II study, an ongoing prospective mortality study, which enrolled approximately 1.2 million adults in 1982. Participants completed a questionnaire detailing individual risk factor data (age, sex, race, weight, height, smoking history, education, marital status, diet, alcohol consumption, and occupational exposures). The risk factor data for approximately 500 000 adults were linked with air pollution data for metropolitan areas throughout the United States and combined with vital status and cause of death data through December 31, 1998.
All-cause, lung cancer, and cardiopulmonary mortality.
Fine particulate and sulfur oxide--related pollution were associated with all-cause, lung cancer, and cardiopulmonary mortality. Each 10-microg/m(3) elevation in fine particulate air pollution was associated with approximately a 4%, 6%, and 8% increased risk of all-cause, cardiopulmonary, and lung cancer mortality, respectively. Measures of coarse particle fraction and total suspended particles were not consistently associated with mortality.
Long-term exposure to combustion-related fine particulate air pollution is an important environmental risk factor for cardiopulmonary and lung cancer mortality.
The mechanism of tissue injury after exposure to air pollution particles is not known. The biological effect has been postulated to be mediated via an oxidative stress catalyzed by metals present in particulate matter (PM). We utilized a transgenic (Tg) mouse model that overexpresses extracellular superoxide dismutase (EC-SOD) to test the hypothesis that lung injury after exposure to PM results from an oxidative stress in the lower respiratory tract. Wild-type (Wt) and Tg mice were intratracheally instilled with either saline or 50 microg of residual oil fly ash (ROFA). Twenty-four hours later, specimens were obtained and included bronchoalveolar lavage (BAL) and lung for both homogenization and light histopathology. After ROFA exposure, EC-SOD Tg mice showed a significant reduction in BAL total cell counts (composed primarily of neutrophils) and BAL total protein compared with Wt. EC-SOD animals also demonstrated diminished concentrations of inflammatory mediators in BAL. There was no statistically significant difference in BAL lipid peroxidation; however, EC-SOD mice had lower concentrations of oxidized glutathione in the BAL. We conclude that enhanced EC-SOD expression decreased both lung inflammation and damage after exposure to ROFA. This supports a participation of oxidative stress in the inflammatory injury after PM exposure rather than reflecting a response to metals alone.
Inhalation of residual oil fly ash (ROFA) increases pulmonary morbidity in exposed workers. We examined the role of reactive oxygen species (ROS) in ROFA-induced lung injury. ROFA was collected from a precipitator at Boston Edison Co., Everett, MA, USA. ROFA (ROFA-total) was suspended in saline, incubated for 24 h at 37 degrees C, centrifuged, and separated into its soluble (ROFA-sol.) and insoluble (ROFA-insol.) fractions. Sprague-Dawley rats were intratracheally instilled with saline or ROFA-total or ROFA-sol. or ROFA-insol. (1 mg/100 g body wt.). Lung tissue and bronchoalveolar lavage cells were harvested at 4, 24, and 72 h after instillation. Chemiluminescence (CL) of recovered cells was measured as an index of ROS production, and tissue-lipid-peroxidation was assessed to determine oxidative injury. Significant amounts of Al, Fe, and Ni were present in ROFA-sol., whereas ROFA-insol. contained Fe, V, and Al. Using electron spin resonance (ESR), significantly more hydroxyl radicals were measured in ROFA-sol. as compared to ROFA-insol. None of the ROFA samples had an effect on CL or lipid peroxidation at 4 h. Treatment with ROFA-total and ROFA-insol. caused significant increases in both CL (at 24 h) and lipid peroxidation (at 24 and 72 h) when compared to saline control value. ROFA-sol. significantly reduced CL production at 72 h after treatment and had no effect on lipid peroxidation at any time point. In summary, ROFA, particularly its soluble fraction, generated a metal-dependent hydroxyl radical as measured by a cell-free ESR assay. However, cellular oxidant production and tissue injury were observed mostly with the ROFA-total and ROFA-insol. particulate forms. ROS generated by ROFA-sol. as measured by ESR appear not to play a major role in the lung injury caused after ROFA exposure.
In this study, we explored the role of chronic exposure to urban air pollution in causing DNA damage (micronuclei frequency in peripheral erythrocytes) in rodents in vivo. Mice (n=20) were exposed to the urban atmosphere of São Paulo for 120 days (February to June 1999) and compared to animals (n=20) maintained in the countryside (Atibaia) for the same period. Daily levels of inhalable particles (PM10), CO, NO(2), and SO(2), were available for São Paulo. Occasional measurements of CO and O(3) were made in Atibaia, showing negligible levels of pollution in the area. The frequency of micronuclei (repeated-measures ANOVA) increased with aging, the highest values obtained for the 90th day of experiment (P<0.001). The exposure to urban air pollution elicited a significant (P=0.016) increase of micronuclei frequency, with no significant interaction with time of study. Associations (Spearman's correlation) between pollution levels of the week that precede blood sampling and micronuclei counts were observed in São Paulo. The associations between micronuclei counts and air pollution were particularly strong for pollutants associated with automotive emissions, such as CO (P=0.037), NO(2) (P<0.001), and PM10 (P<0.001). Our results support the concept that urban levels of air pollution may cause somatic mutations.
Exposure to ambient air pollution particles (PM) has been associated with increased cardiopulmonary morbidity and mortality, particularly in individuals with pre-existing disease. Exacerbation of pulmonary inflammation in susceptible people (e.g., asthmatics, COPD patients) appears to be a central mechanism by which PM exert their toxicity. Health effects are seen most consistently with PM with aerodynamic diameter < 2.5 micrometers (PM(2.5)), although 10 micrometers < PM < 2.5 micrometers can also be toxic. Through its metal, semi-quinone, lipopolysaccaride, hydrocarbon, and ultrafine constituents, PM may exert oxidative stress on cells in the lung by presenting or by stimulating the cells to produce reactive oxygen (ROS). In vivo, PM increase cytokine and chemokine release, lung injury, and neutrophil influx. In vitro analysis of PM effects on the critical cellular targets, alveolar macrophages, epithelial cells, and neutrophils, demonstrates PM- and oxidant-dependent responses consistent with in vivo data. These effects have been observed with PM samples collected over years as well as concentrated PM(2.5) (CAPs) collected in real time. Oxidative stress mediated by ROS is an important mechanism of PM-induced lung inflammation.
PM10 is a complex mixture of particles and we have focused here on the ultrafine component, i.e. particles with a diameter of less than 100 nm. In PM10 this fraction is mostly composed of combustion-derived, carbon-centred particles with associated hydrocarbons and metals. Progress in understanding the effects of ultrafine particles in the lungs has been achieved largely through the use of surrogate particles such as ultrafine carbon black and titanium dioxide. Using these types of particles, ultrafines have been shown to cause oxidative stress and pro-inflammatory effects in a number of in vivo and in vitro models. The mechanisms of the generation of the oxidative stress is not understood, but appears to be related to the large particle surface area in some way. Modulation of calcium signalling also appears to be involved in the stimulation of cytokine release by macrophages in response to ultrafines. Effects of PM10 are seen on cardiovascular mortality and morbidity, as well as on the lung. Although the role of ultrafine particles in these effects are not well understood there are plausible pathways that remain to be explored.
Urban and industrial air pollution can cause elevated heritable mutation rates in birds and rodents. The relative importance of airborne particulate matter versus gas-phase substances in causing these genetic effects under ambient conditions has been unclear. Here we show that high-efficiency particulate-air (HEPA) filtration of ambient air significantly reduced heritable mutation rates at repetitive DNA loci in laboratory mice housed outdoors near a major highway and two integrated steel mills. These findings implicate exposure to airborne particulate matter as a principal factor contributing to elevated mutation rates in sentinel mice and add to accumulating evidence that air pollution may pose genetic risks to humans and wildlife.
Air pollution is associated with an increased risk of lung cancer and has other adverse health effects. In their Perspective, [Samet, DeMarini, and Malling][1] discuss new findings ([ Somers et al .][2]) showing that particulate air pollution can induce presumptive mutations in the germline cells of male mice that can be passed on to the next generation. The germline mutation rate was reduced by about 50% if the mice were exposed to air cleansed of particulate matter by passage through a HEPA filter.
[1]: http://www.sciencemag.org/cgi/content/full/304/5673/971
[2]: http://www.sciencemag.org/cgi/content/short/304/5673/1008
In 1998 Congress mandated expanded U.S. Environmental Protection Agency (U.S. EPA) health effects research on ambient air particulate matter (PM) and a National Research Council (NRC) committee to provide research oversight. The U.S. EPA currently supports intramural and extramural PM research, including five academically based PM centers. The PM centers in their first 2.5 years have initiated research directed at critical issues identified by the NRC committee, including collaborative activities, and sponsored scientific workshops in key research areas. Through these activities, there is a better understanding of PM health effects and scientific uncertainties. Future PM centers research will focus on long-term effects associated with chronic PM exposures. This report provides a synopsis of accomplishments to date, short-term goals (during the next 2.5 years) and longer-term goals. It consists of six sections: biological mechanisms, acute effects, chronic effects, dosimetry, exposure assessment, and the specific attributes of a coordinated PM centers program.
It is important to characterize the chemical properties of particulate matter in order to understand how low doses, inhaled by a susceptible population, might cause human health effects. The formation of reactive oxygen species catalyzed by neutral, aqueous extracts of two ambient particulate samples, National Institute of Standards & Technology (NIST) Standard Reference Materials (SRM) 1648 and 1649, and two diesel particulate samples, NIST SRM 1650 and SRM 2975, were measured. The formation of reactive oxygen species was estimated by measuring the formation of malondialdehyde from 2-deoxyribose in the presence of ascorbic acid; H2O2 was not added to this assay. SRM 1649, ambient particulate matter collected from Washington, DC, generated the most malondialdehyde, while SRM 2975, diesel particulate matter collected from a forklift, yielded the least amount. Desferrioxamine inhibited the formation of malondialdehyde from the particulate samples providing additional data to support the observation that transition metals were involved in the generation of reactive oxygen species. Six transition metal sulfates (iron sulfate, copper sulfate, vanadyl sulfate, cobalt sulfate, nickel sulfate, and zinc sulfate) were assayed for their ability to generate reactive oxygen species under the same conditions used for the particulate samples in order to facilitate comparisons between particles and these transition metals. The concentration of transition metals was measured in aqueous extracts of these particulate samples using ion-coupled plasma mass spectrometry (ICP-MS) analysis. There was qualitative agreement between the concentrations of Fe, Cu, and V and the amount of malondialdehyde produced from extracts of these particulate samples. These data suggest that transition metals can be dissolved from particles in neutral, aqueous solutions and that these metals are capable of catalyzing the formation of reactive oxygen species.
Epidemiological studies have reported a positive association of short-term increases in ambient particulate matter (PM) with daily mortality and hospital admissions for cardiovascular disease. Although patients with cardiopulmonary disease appear to be most at risk, particulate-related cardiac effects following myocardial infarction (MI) have not been examined. To improve understanding of mechanisms, we developed and tested a model for investigating the effects of inhaled PM on arrhythmias and heart rate variability (HRV), a measure of autonomic nervous system activity, in rats with acute MI. Left-ventricular MI was induced in 31 Sprague-Dawley rats by thermocoagulation of the left coronary artery; 32 additional rats served as sham-operated controls. Diazepam-sedated rats were exposed (1 h) to residual oil fly ash (ROFA), carbon black, or room air at 12-18 h after surgery. Each exposure was immediately preceded and followed by a 1-h exposure to room air (baseline and recovery periods, respectively). Lead-II electrocardiograms were recorded. In the MI group, 41% of rats exhibited one or more premature ventricular complexes (PVCs) during the baseline period. Exposure to ROFA, but not to carbon black or room air, increased arrhythmia frequency in animals with preexisting PVCs. Furthermore, MI rats exposed to ROFA, but not to carbon black or room air, decreased HRV. There was no difference in arrhythmia frequency or HRV among sham-operated animals. These results underscore the usefulness of this model for elucidating the physiologic mechanisms of pollution-induced cardiovascular arrhythmias and contribute to defining the specific constituents of ambient particles responsible for arrhythmias.
Diesel exhaust particles (DEP) induce pulmonary diseases in- cluding asthma and chronic bronchitis. Comprehensive evaluation is required to know the effects of pollutants including DEP on these and other lung diseases. Alveolar macrophages (AM) and epithelial cells are important cellular targets for pollutants such as DEP in the lung. Alveolar macrophages encounter and phagocy- tose DEP in the alveolar space, and their biological responses have been implicated in DEP-induced pulmonary diseases. Expression profiles of genes induced by DEP in AM will lead to better under- standing of the mechanisms involved in pulmonary diseases. To characterize the effect of the DEP extract on AM systematically, we analyzed the gene expression in AM exposed to DEP extract using the Atlas Rat Toxicology Array II. The finding in cDNA microarray was further confirmed by Northern blot analysis. AM were exposed to 10 mg/ml of DEP extract fo r6hi norder to elucidate early response to DEP extract in AM. Early response to DEP extract in AM may affect the alteration of gene expression in subsequent responses so that it is important to identify the alter- ation in early response. In this study, the transcription of 6 genes in the cDNA microarray was significantly elevated by exposure of the AM to DEP extract. These genes were heme oxygenase (HO)-1 and -2, thioredoxin peroxidase 2 (TDPX-2), glutathione S-trans- ferase P subunit (GST-P), NAD(P)H dehydrogenase, and prolif- erating cell nuclear antigen (PCNA). The antioxidative enzymes such as HO, TDPX-2, GST-P, and NAD(P)H dehydrogenase may play a role in the pulmonary defense against oxidative stress caused by various pollutants including DEP. PCNA may have contributed to the repair of DNA damage and to cell proliferation caused by exposure to these pollutants. Our results suggest that cDNA microarray analysis is a useful tool to investigate the bio-
Alveolar macrophages (AMs) occupy a key position in silica-induced pulmonary fibrosis, although the mechanisms are yet to be elucidated. In the present study we examined the involvement of oxidative stress and reactive oxygen species formation in silica-induced cytotoxicity and genotoxicity in cultured rat AMs. A lucigenin-dependent chemiluminescence test was used to determine superoxide anion (O−2), and a 2′,7′-dichlorofluorescin diacetate fluorescence test was employed to measure the hydrogen peroxide (H2O2) level. The cytotoxic and genotoxic effects caused by silica in AMs were examined by lactate dehydrogenase (LDH) leakage and single-cell gel electrophoresis (comet assay), respectively. The results showed that silica enhanced O−2 and H2O2 formation in AMs. There were clear dose- and time-dependent relationships in silica-induced cytotoxicity and genotoxicity. Furthermore, superoxide dismutase and catalase were able to reduce silica-induced LDH leakage and DNA damage, with concurrent significant inhibition on silica-induced oxidative stress in AMs. These findings provide convincing evidence that oxidative stress mediates the silica-induced cytotoxicity and genotoxicity. The understanding of such a mechanism may provide a scientific basis for the possible application of antioxidants in preventing the hazardous effects of silica.
X-ray absorption fine structure (XAFS) spectra for S, Cl, V, Cr, Mn, Cu, Zn, As, Br, Cd and Pb and Mössbauer spectra for Fe have been obtained for two National Institute of Standards and Technology (NIST) particulate matter (PM) standard reference materials (SRMs): urban PM (SRM 1648) and diesel PM (SRM 1650). The spectral data, complemented by information on elemental concentrations from proton-induced X-ray-emission (PIXE) spectroscopy, were used to interpret the speciation of these elements in these complex materials. It appears that all the metallic elements investigated occur in oxidized forms, principally as sulfates in the diesel PM SRM and as sulfates, oxides, and possibly other forms (e.g. clays?) in the urban PM. A minor fraction of the sulfur and major fractions of the halogens, Cl and Br, occur as organosulfide (thiophene) and organohalide occurrences, respectively, that must be associated with the abundant carbonaceous matter that constitutes the major component of the two PM SRMs. Most of the sulfur, however, occurs as sulfate in the urban PM and as bisulfate in the diesel PM. In addition, elemental oxidation states have been determined directly by the spectroscopic techniques. Such information is often the key parameter in determining the toxicity and solubility of specific elements in PM, both of which are important in understanding the threat that such elements may pose to human health. For the two HAP elements, Cr and As, for which the toxicity depends greatly on oxidation state, the XAFS data showed that both elements are present in both SRMs predominantly in the less toxic oxidation states, Cr(III) and As(V). The potential of the XAFS spectra for use as source apportionment signatures is illustrated by reference to chromium, which exists in these two PM SRMs in very different forms.
This paper reviews the field of biosensors in which the biological component consists of living cells. One of the most important reasons for using living cells is to obtain functional information, i.e. information about the effect of a stimulus on a living system. In many cases, functional rather than analytical information is ultimately desired. Whole-cell biosensors provide the opportunity to elicit such information, for applications such as pharmacology, cell biology, toxicology, and environmental measurements. One particularly important application is drug discovery, where the binding assays that are commonly used to provide high throughput need to be complemented with a functional assay. A micromachined silicon chip that is capable of providing a high throughput functional assay based on extracellular acidification is described.
The role of reactive oxygen species, with the subsequent oxidative deterioration of biological macromolecules in the toxicities associated with transition metal ions, is reviewed. Recent studies have shown that metals, including iron, copper, chromium, and vanadium undergo redox cycling, while cadmium, mercury, and nickel, as well as lead, deplete glutathione and protein-bound sulfhydryl groups, resulting in the production of reactive oxygen species as superoxide ion, hydrogen peroxide, and hydroxyl radical. As a consequence, enhanced lipid peroxidation. DNA damage, and altered calcium and sulfhydryl homeostasis occur. Fenton-like reactions may be commonly associated with most membranous fractions including mitochondria, microsomes, and peroxisomes. Phagocytic cells may be another important source of reactive oxygen species in response to metal ions. Furthermore, various studies have suggested that the ability to generate reactive oxygen species by redox cycling quinones and related compounds may require metal ions. Recent studies have suggested that metal ions may enhance the production of tumor necrosis factor alpha (TNF alpha) and activate protein kinase C, as well as induce the production of stress proteins. Thus, some mechanisms associated with the toxicities of metal ions are very similar to the effects produced by many organic xenobiotics. Specific differences in the toxicities of metal ions may be related to differences in solubilities, absorbability, transport, chemical reactivity, and the complexes that are formed within the body. This review summarizes current studies that have been conducted with transition metal ions as well as lead, regarding the production of reactive oxygen species and oxidative tissue damage.
Identification of constituents responsible for the pulmonary toxicity of fugitive combustion emission source particles may provide insight into the adverse health effects associated with exposure to these particles as well as ambient air particulate pollution. Herein, we describe results of studies conducted to identify constituents responsible for the acute lung injury induced by residual oil fly ash (ROFA) and to assess physical-chemical factors that influence the pulmonary toxicity of these constituents. Biochemical and cellular analyses performed on bronchoalveolar lavage fluid obtained from rats following intratracheal instillation of ROFA suspension demonstrated the presence of severe inflammation, an indicator of pulmonary injury, which included recruitment of neutrophils, eosinophils, and monocytes into the airway. A leachate prepared from ROFA, containing predominantly Fe, Ni, V, Ca, Mg, and sulfate, produced similar lung injury to that induced by ROFA suspension. Depletion of Fe, Ni, and V from the ROFA leachate abrogated its pulmonary toxicity. Correspondingly, minimal lung injury was observed in animals exposed to saline-washed ROFA particles. A surrogate transition metal sulfate solution containing Fe, V, and Ni largely reproduced the lung injury induced by ROFA. Metal interactions and pH were found to influence the severity and kinetics of lung injury induced by ROFA and soluble transition metals. These findings provide direct evidence for the role of soluble transition metals in the pulmonary injury induced by the combustion emission source particulate, ROFA.
Although the tachykinins substance P (SP) and neurokinin A have been largely localized to neurons, eosinophils have also been shown to express these peptides. Our aim was to determine whether rat alveolar macrophages (AM) express preprotachykinin gene-I (PPT-I) mRNA that encodes these tachykinins and to examine expression during inflammation. PPT-I mRNA was detected by reverse transcription (RT)-polymerase chain reaction (PCR) in AM and brain (control) but not in peritoneal macrophages. Northern analysis showed that PPT-I mRNA was induced two- to fourfold by in vivo treatment of rats with intratracheal lipopolysaccharide (LPS) and in vitro after 4 h of exposure to LPS. This increase was inhibited by dexamethasone. In situ RT-PCR and immunocytochemistry further confirmed that AM express PPT-I mRNA and SP-like immunoreactivity, respectively, which was enhanced by LPS treatment. A 1.3-kb transcript consistent with PPT-I mRNA was detected by Northern analysis of bronchoalveolar lavage neutrophils. Therefore, rat AM express PPT-I mRNA that is upregulated in AM by LPS and is attenuated by dexamethasone. PPT-I mRNA was also detected in lung neutrophils.
Occupational exposure to residual oil fly ash (ROFA) particulate has been associated with adverse respiratory health effects in humans. We hypothesized that ROFA collected at different sites within an oil burning power plant, by virtue of its differing metal and sulfate composition, will induce differential lung injury. Ten ROFA samples collected at various sites within a power plant were analyzed for water- and 1.0 M HCl-leachable arsenic (As), beryllium (Be), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), vanadium (V), zinc (Zn), and sulfur by inductively coupled plasma-atomic emission spectroscopy. All ROFA samples contained variable amounts of leachable (water-extractable) and 1.0 M HCl-extractable Fe, V, and/or Ni. All other metals, except Zn (ROFA No. 1 contained 3.43 and No. 3, 6.35 micrograms/mg Zn), were present in negligible quantities (< 1.0 microgram/mg) in the water extract. In vivo pulmonary injury from exposure to whole saline suspensions of these ROFA was evaluated. Male, SD rats (60 days old) were intratracheally instilled with either saline or saline suspension of whole ROFA (< 3.0 mass median aerodynamic diameter) at three concentrations (0.833, 3.33, or 8.33 mg/kg). After 24 h, lungs were lavaged and bronchoalveolar lavage fluid (BALF) was analyzed for cellular influx and protein content as well as lactate dehydrogenase (LDH) and N-acetyl glucosaminidase (NAG) activity and total hemoglobin as indicators of lung injury. ROFA-induced increases in BALF protein and LDH, but not neutrophilic inflammation, were associated with its water-leachable total metal, Ni, Fe, and sulfate content. However, the neutrophilic response following ROFA exposure was positively correlated with its water-leachable V content. Modest lung injury was observed with the ROFA samples which contained the smallest amounts of water-leachable metals. The ability of ROFA to induce oxidative burst in alveolar macrophage (AM) was determined in vitro using a chemiluminescence (CL) assay. AM CL signals in vitro were greatest with ROFA containing primarily soluble V and were less with ROFA containing Ni plus V. In summary, ROFA-induced in vivo acute pulmonary inflammation appears to be associated with its water-leachable V content; however, protein leakage appears to be associated with its water-leachable Ni content. ROFA-induced in vitro activation of AM was highest with ROFA containing leachable V but not with Ni plus V, suggesting that the potency and the mechanism of pulmonary injury will differ between emissions containing V and Ni.
Current biosensor developments can be summarised by different trends. For traditional enzymatic biosensors such as glucose sensors, steady improvements of well known basic principles have been made in order to achieve better sensor stability. On the other hand, new affinity sensors such as nucleic acid sensors, transmembrane sensors, and sensors utilising whole cells or even cell networks have become of increasing interest. New ways to miniaturise biosensors and to control their interfaces down to the molecular level have been introduced (the bioelectronics approach). High-throughput screening based on various signal transduction principles has become of increasing importance.
Diesel exhaust particles (DEP) contain organic chemicals that contribute to the adverse health effects of inhaled particulate matter. Because DEP induce oxidative stress in the lung and in macrophages, effective antioxidant defenses are required. One type of defense is through the expression of the antioxidant enzyme, heme oxygenase I (HO-1). HO-1 as well as phase II detoxifying enzymes are induced via antioxidant response elements (ARE) in their promoters of that gene. We show that a crude DEP total extract, aromatic and polar DEP fractions, a benzo(a)pyrene quinone, and a phenolic antioxidant induce HO-1 expression in RAW264.7 cells in an ARE-dependent manner. N-acetyl cysteine and the flavonoid, luteolin, inhibited HO-1 protein expression. We also demonstrate that the same stimuli induce HO-1 mRNA expression in parallel with the activation of the SX2 enhancer of that gene. Mutation of the ARE core, but not the overlapping AP-1 binding sequence, disrupted SX2 activation. Finally, we show that biological agents, such as oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, could also induce HO-1 expression via an ARE-dependent mechanism. Prior induction of HO-1 expression, using cobalt-protoporphyrin, protected RAW264.7 cells against DEP-induced toxicity. Taken together, these data show that HO-1 plays an important role in cytoprotection against redox-active DEP chemicals, including quinones.
It is important to characterize the chemical properties of particulate matter in order to understand how low doses, inhaled by a susceptible population, might cause human health effects. The formation of reactive oxygen species catalyzed by neutral, aqueous extracts of two ambient particulate samples, National Institute of Standards & Technology (NIST) Standard Reference Materials (SRM) 1648 and 1649, and two diesel particulate samples, NIST SRM 1650 and SRM 2975, were measured. The formation of reactive oxygen species was estimated by measuring the formation of malondialdehyde from 2-deoxyribose in the presence of ascorbic acid; H2O2 was not added to this assay. SRM 1649, ambient particulate matter collected from Washington, DC, generated the most malondialdehyde, while SRM 2975, diesel particulate matter collected from a forklift, yielded the least amount. Desferrioxamine inhibited the formation of malondialdehyde from the particulate samples providing additional data to support the observation that transition metals were involved in the generation of reactive oxygen species. Six transition metal sulfates (iron sulfate, copper sulfate, vanadyl sulfate, cobalt sulfate, nickel sulfate, and zinc sulfate) were assayed for their ability to generate reactive oxygen species under the same conditions used for the particulate samples in order to facilitate comparisons between particles and these transition metals. The concentration of transition metals was measured in aqueous extracts of these particulate samples using ion-coupled plasma mass spectrometry (ICP-MS) analysis. There was qualitative agreement between the concentrations of Fe, Cu, and V and the amount of malondialdehyde produced from extracts of these particulate samples. These data suggest that transition metals can be dissolved from particles in neutral, aqueous solutions and that these metals are capable of catalyzing the formation of reactive oxygen species.
We are in the midst of a biotechnology revolution. Significant advances have been made in sensors and diagnostics based on interrogation of biomolecular arrays. The surface conjugation of nucleic acids, antibodies and proteins onto 'chip' formats has resulted in new classes of high information content devices. This compilation of articles presents the emergence of a new class of such devices based on the ability to interrogate cellular or tissue microarrays. Unlike nucleic acid or antibody-based approaches, these systems enable the interrogation of more complex biological responses, and offer the potential to gather higher information content from measuring physiologic, metabolic, or network processes and responses. This endeavor presents many technological challenges but offers the promise of collecting information more closely correlated to human response and as such represents the opportunity to fabricate new sensors and diagnostics for environmental detection and medical diagnostics.
Epidemiological studies have reported a positive association of short-term increases in ambient particulate matter (PM) with daily mortality and hospital admissions for cardiovascular disease. Although patients with cardiopulmonary disease appear to be most at risk, particulate-related cardiac effects following myocardial infarction (MI) have not been examined. To improve understanding of mechanisms, we developed and tested a model for investigating the effects of inhaled PM on arrhythmias and heart rate variability (HRV), a measure of autonomic nervous system activity, in rats with acute MI. Left-ventricular MI was induced in 31 Sprague-Dawley rats by thermocoagulation of the left coronary artery; 32 additional rats served as sham-operated controls. Diazepam-sedated rats were exposed (1 h) to residual oil fly ash (ROFA), carbon black, or room air at 12-18 h after surgery. Each exposure was immediately preceded and followed by a 1-h exposure to room air (baseline and recovery periods, respectively). Lead-II electrocardiograms were recorded. In the MI group, 41% of rats exhibited one or more premature ventricular complexes (PVCs) during the baseline period. Exposure to ROFA, but not to carbon black or room air, increased arrhythmia frequency in animals with preexisting PVCs. Furthermore, MI rats exposed to ROFA, but not to carbon black or room air, decreased HRV. There was no difference in arrhythmia frequency or HRV among sham-operated animals. These results underscore the usefulness of this model for elucidating the physiologic mechanisms of pollution-induced cardiovascular arrhythmias and contribute to defining the specific constituents of ambient particles responsible for arrhythmias.
Diesel exhaust particles (DEP) induce pulmonary diseases including asthma and chronic bronchitis. Comprehensive evaluation is required to know the effects of pollutants including DEP on these and other lung diseases. Alveolar macrophages (AM) and epithelial cells are important cellular targets for pollutants such as DEP in the lung. Alveolar macrophages encounter and phagocytose DEP in the alveolar space, and their biological responses have been implicated in DEP-induced pulmonary diseases. Expression profiles of genes induced by DEP in AM will lead to better understanding of the mechanisms involved in pulmonary diseases. To characterize the effect of the DEP extract on AM systematically, we analyzed the gene expression in AM exposed to DEP extract using the Atlas Rat Toxicology Array II. The finding in cDNA microarray was further confirmed by Northern blot analysis. AM were exposed to 10 microg/ml of DEP extract for 6 h in order to elucidate early response to DEP extract in AM. Early response to DEP extract in AM may affect the alteration of gene expression in subsequent responses so that it is important to identify the alteration in early response. In this study, the transcription of 6 genes in the cDNA microarray was significantly elevated by exposure of the AM to DEP extract. These genes were heme oxygenase (HO)-1 and -2, thioredoxin peroxidase 2 (TDPX-2), glutathione S-transferase P subunit (GST-P), NAD(P)H dehydrogenase, and proliferating cell nuclear antigen (PCNA). The antioxidative enzymes such as HO, TDPX-2, GST-P, and NAD(P)H dehydrogenase may play a role in the pulmonary defense against oxidative stress caused by various pollutants including DEP. PCNA may have contributed to the repair of DNA damage and to cell proliferation caused by exposure to these pollutants. Our results suggest that cDNA microarray analysis is a useful tool to investigate the biological responses to pulmonary toxicants.
In vitro studies suggest that reactive oxygen species contribute to the cardiopulmonary toxicity of particulate air pollution. To evaluate the ability of particulate air pollution to promote oxidative stress and tissue damage in vivo, we studied a rat model of short-term exposure to concentrated ambient particles (CAPs). We exposed adult Sprague-Dawley rats to either CAPs aerosols (group 1; average CAPs mass concentration, 300 +/- 60 micro g/m3) or filtered air (sham controls) for periods of 1-5 hr. Rats breathing CAPs aerosols for 5 hr showed significant oxidative stress, determined as in situ chemiluminescence in the lung [group 1, 41 +/- 4; sham, 24 +/- 1 counts per second (cps)/cm2] and heart (group 1, 45 +/- 4; sham, 24 +/- 2 cps/cm2) but not liver (group 1, 10 +/- 3; sham, 13 +/- 3 cps/cm2). Increases in oxidant levels were also triggered by highly toxic residual oil fly ash particles (lung chemiluminescence, 90 +/- 10 cps/cm2; heart chemiluminescence, 50 +/- 3 cps/cm2) but not by particle-free air or by inert carbon black aerosols (control particles). Increases in chemiluminescence showed strong associations with the CAPs content of iron, manganese, copper, and zinc in the lung and with Fe, aluminum, silicon, and titanium in the heart. The oxidant stress imposed by 5-hr exposure to CAPs was associated with slight but significant increases in the lung and heart water content (approximately 5% in both tissues, p < 0.05) and with increased serum levels of lactate dehydrogenase (approximately 80%), indicating mild damage to both tissues. Strikingly, CAPs inhalation also led to tissue-specific increases in the activities of the antioxidant enzymes superoxide dismutase and catalase, suggesting that episodes of increased particulate air pollution not only have potential for oxidant injurious effects but may also trigger adaptive responses.
The regulation of lipopolysaccharide (LPS)-mediated pro-inflammatory cytokine biosynthesis by reduction-oxidation (redox)-sensitive enzymes involved in maintaining intracellular glutathione homeostasis was investigated in fetal alveolar type II epithelial cells (fATII). Inhibition of glutathione-oxidized disulfide reductase, which recycles GSSG --> 2GSH, by the action of 1,3-bis-(2-chloroethyl)-1-nitrosourea (BCNU) augmented LPS-dependent secretion of interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha. BCNU increased [GSSG] concentration at the expense of [GSH], thereby favoring oxidation equilibrium. Inhibition of gamma-glutamylcysteine synthetase, the rate-limiting enzyme in the biosynthesis of GSH, by the action of L-buthionine-(S,R)-sulfoximine (BSO), potentiated LPS-induced IL-1beta, IL-6 and TNF-alpha production. Similar to BCNU, BSO depleted [GSH] and induced the accumulation of [GSSG]. BCNU and BSO reduced LPS-mediated phosphorylation of inhibitory-kappaB (IkappaB-alpha), allowing its cytosolic accumulation. This effect was associated with the inhibition of the nuclear translocation of selective nuclear factor (NF)-kappaB subunits: NF-kappaB1 (p50), RelA (p65), RelB (p68) and c-Rel (p75), but not NF-kappaB2 (p52). BCNU and BSO reduced LPS-induced NF-kappaB activation as determined by the electrophoretic mobility shift DNA-binding assay. Analytical analysis of the effect of modulating the dynamic redox ratio ([GSH]+[GSSG])/[GSSG] revealed a novel role for GSSG as a disulfhydryl compound which mediates an inhibitory effect on NF-kappaB activation. It is concluded that selective modulation of redox-sensitive enzymes has an immunopharmacological potential in regulating pro-inflammatory cytokines and that the TkappaB-alpha/NF-kappaB pathway is redox-sensitive and differentially involved in mediating redox-dependent regulation of cytokine signaling.
Airborne particulate matter (PM) increases morbidity and mortality resulting from cardiopulmonary diseases including cancer. We hypothesized that PM is genotoxic to alveolar epithelial cells (AEC) by causing DNA damage and apoptosis. PM caused dose-dependent AEC DNA strand break formation, reductions in mitochondrial membrane potential (Delta psi m), caspase 9 activation, and apoptosis. An iron chelator and a free radical scavenger prevented these effects. Finally, overexpression of Bcl-xl, a mitochondrial anti-apoptotic protein, blocked PM-induced Delta psi m and DNA fragmentation. We conclude that PM causes AEC DNA damage and apoptosis by mechanisms that involve the mitochondria-regulated death pathway and the generation of iron-derived free radicals.
Inhalation exposure to urban air particles is known to increase morbidity in humans and animals. Our group utilizes the Harvard/U.S. Environmental Protection Agency Ambient Particle Concentrator (HAPC) to generate concentrated aerosols of outdoor air particles for experimental exposures. We have reported increased pathologic responses to inhalation of concentrated urban air particles and identified silicon (as silicate) as an element associated with many of these responses. Using silicate-rich Mt. St. Helen's volcanic ash (MSHA), we exposed three groups of Sprague-Dawley rats by inhalation for 6 hr to filtered air, MSHA, or MSHA passed though the HAPC. Twenty-four hours following exposure, bronchoalveolar lavage was performed to assess total cell count, differential cell count, protein, lactate dehydrogenase, and n-beta-glucosaminidase levels. Peripheral blood was examined for packed cell volume, total protein, total white cells, and differential cell count. Morphologic studies localized particles in the lung and assessed pulmonary vasculature. No significant differences were observed among any of the groups in any parameter measured including morphometric analysis of pulmonary vasoconstriction. Scanning electron microscopy and X-ray analysis identified particles as silicates typical of MSHA throughout the lung. These findings suggest that particles passing through the HAPC have no change in their toxic potential in an exposure setting where particle deposition in the lung has occurred.
Several epidemiological studies have consistently demonstrated significant associations between ambient levels of particulate matter and lung injury and cardiovascular events with increased morbidity and mortality. Particle surrogates (PS), such as residual oil fly ash (ROFA), have been widely used in experimental studies aimed at characterizing the mechanisms of particle toxicity. Since PS composition varies depending on its source, studies with different types of PS may provide clues about the relative toxicity of the components generated by high-temperature combustion process. In this work, we have studied the effects of nasal instillation of increasing doses of different PS in mice: saline, carbon, and two types of particle surrogates. PS type A (PSA) was the ROFA collected from the waste incinerator of our university hospital; PS type B (PSB) was collected from the electrostatic precipitator of a large steel company and thus had an elevated metal content. After 24h, we analyzed hematological parameters, fibrinogen, bronchoalveolar lavage, bone marrow, and pulmonary histology. Nasal instillation of the two types of PS-induced leucopenia. PSB elicited a greater elevation of plasma fibrinogen levels. Bone marrow and pulmonary inflammatory changes were more intense for PSA. We concluded that the PS composition modulates acute inflammatory changes more significantly than the mass for these two types of PS.
Urban suspended particulate pollutants differ with place of occurrence, meteorological conditions, physicochemical compositions, and the response of the bronchopulmonary apparatus. Lung injury following intratracheal instillation of respirable suspended particulate matter (RSPM) collected in an urban setting in India was investigated in rats. The animals were killed 15 days after exposure to 2.5, 5.0, and 10.0 mg of RSPM. We examined the changes in lung histology, enzymatic activity in the bronchoalveolar lavage (BAL), and the oxidant/ antioxidant status in lung homogenates. The alterations in these parameters were compared with those in rats instilled with quartz particulates, which were used as positive controls. Exposure to RSPM resulted in an increase in the relative weight of lungs and inflammatory changes evidenced by an increase in the total cellularity of the lungs, predominantly polymorphonuclear cells, demonstrable both in the lungs sections and in the bronchoalveolar lavage of the exposed animals. An increase in the protein content and in the lactate dehydrogenase activity in the BAL was found in the RSPM-exposed rats. A marked increase in the output of lipid peroxides and a dose-dependent increase in the formation of reactive nitrogen species (NO) in lung homogenates and BAL, respectively, was found in the RSPM-exposed rats. A significant decrease in the enzymatic lung antioxidants, superoxide dismutase, and catalase was observed. However, the alterations in the levels of glutathione in the lungs of the RSPM-exposed animals were not significant. The inflammatory reaction, oxidative changes, and enzyme release, were more marked in quartz-exposed animals in comparison to the RSPM-exposed rats.
Exposure to increased levels of ambient particulate matter (PM) are associated with several health effects, including cardiopulmonary diseases. The formation of reactive oxygen species (ROS) is thought to play an important role in the induction of these health effects. To quantify the ROS generating capacityof PM,we developed an improved electron spin resonance (ESR) spectrometry-based method. ROS formation was measured directly on PM-containing filters, thereby avoiding the selective extraction of components and loss of material or reactivity, which is likely to occur during filter extraction. Also, ascorbic acid was added to stimulate ROS formation. This method was applied to PM10 samples originating from different sources. The radical generating capacity of PM10 from both gasoline and diesel engine exhaust was significantly higher as compared to that of PM10 from ambient or indoor air. Furthermore, in urban PM10 and PM2.5, ROS-generating capacity significantly correlated with concentrations of polycyclic aromatic hydrocarbon content and particular transition metals. This indicates thatthis improved ESR method may be a valuable tool for evaluating the relationship between ROS formation by PM and the adverse health effects associated with this type of air pollution.
This paper reviews the field of biosensors in which the biological component consists of living cells. One of the most important reasons for using living cells is to obtain functional information, i.e. information about the effect of a stimulus on a living system. In many cases, functional rather than analytical information is ultimately desired. Whole-cell biosensors provide the opportunity to elicit such information, for applications such as pharmacology, cell biology, toxicology, and environmental measurements. One particularly important application is drug discovery, where the binding assays that are commonly used to provide high throughput need to be complemented with a functional assay. A micromachined silicon chip that is capable of providing a high throughput functional assay based on extracellular acidification is described.
Health EffectsResearchCentersProgram: amidcoursereportofstatus, progress,andplans
- M Lippmann
- M Frampton
- J Schwartz
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- R Schlesinger
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- J Froines
- A Nel
- J Finkelstein
- J Godleski
- J Kaufman
- J Koenig
- T Larson
- D Luchtel
- L J Liu
- G Oberdorster
- A Peters
Lippmann, M.; Frampton, M.; Schwartz, J.; Dockery, D.; Schlesinger, R.; Koutrakis, P.; Froines, J.; Nel, A.; Finkelstein, J.; Godleski, J.; Kaufman, J.; Koenig, J.; Larson, T.; Luchtel, D.; Liu, L. J.; Oberdorster, G.; Peters, A.; Sarnat, J.; Sioutas, C.; Suh, H.; Sullivan, J.; Utell, M.; Wichmann, E.; Zelikoff, J. The U.S. Environmental Protection Agency Particulate Matter Health EffectsResearchCentersProgram: amidcoursereportofstatus, progress,andplans.Environ.HealthPerspect.2003,111,1074- 1092.
TheH2-18O-inorganic phosphate and H2-18O-adenosine triphosphate ex-changereactionsinsubmitochondrialparticlesfrombeefheart Received for review September 21 Revised manuscript received February 6
- P C Hinkle
- H S Penefsky
- E Racker
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Hinkle,P.C.;Penefsky,H.S.;Racker,E.Partialresolutionofthe enzymescatalyzineoxidativephosphorylation.XII.TheH2-18O-inorganic phosphate and H2-18O-adenosine triphosphate ex-changereactionsinsubmitochondrialparticlesfrombeefheart. J. Biol. Chem. 1967, 242, 1788-1792. Received for review September 21, 2005. Revised manuscript received February 6, 2006. Accepted February 7, 2006. ES0518732 VOL. 40, NO. 8, 2006 / ENVIRONMENTAL SCIENCE & TECHNOLOGY92811
Currenthypothesesonthemechanisms oftoxicityofultrafineparticles
- K Donaldson
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EnvironmentalProtection AgencyAmbientParticleConcentratorchangethetoxicpotential of particles?
- S T Savage
- J Lawrence
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- R C Stearns
- B A Coull
- J J Godleski
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