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The protective effect of p-Coumaric acid on hepatic injury caused by particulate matter in the rat and determining the role of long noncoding RNAs MEG3 and HOTAIR
Abstract
Increasing air pollution is associated with serious human health problems. P-coumaric acid (PC) is a herbal phenolic compound that exhibits beneficial pharmacological potentials. Here, the protective effect of PC on liver injury induced by air pollution was examined. Thirty-two adult male Wistar rats (200-250 g) were divided randomly into four groups (n = 8). The groups were; Control (rats received DMSO and then exposed to clean air), PC (rats received PC and then exposed to clean air), DMSO + Dust (rats received DMSO and then exposed to dust), and PC + Dust (the animals received PC and then exposed to dust). The clean air, DMSO, PC, and dust were administrated 3 days a week for 6 consecutive weeks. The rats were anesthetized and their blood samples and liver sections were taken to conduct molecular, biomedical, and histopathological tests. Dust exposure increased the liver enzymes, bilirubin, triglyceride, cholesterol, and the production of liver malondialdehyde, and decreased in liver total anti-oxidant capacity and serum high-density lipoprotein. It also increased the mRNA expression of inflammatory-related cytokines, decreased the mRNA expression of SIRT-1, decreased the expression levels of miR-20b5p, and MEG3 while increased the expression levels of miR-34a, and HOTAIR. Dust exposure also increased the liver content of three cytokines TNF-α, NF-κB, HMGB-1, and ATG-7 proteins. PC enhanced liver function against adverse effects of dust through recovering almost all the studied variables. Exposure to dust damaged the liver through induction of oxidative stress, inflammation, and autophagy. PC protected the liver against dust-induced cytotoxicity.
The ultimate fate of Graafian follicles is ovulation or atresia which relies on the highly coordinated processes of apoptosis and autophagy in ovarian cells. Long non-coding RNA maternally expressed gene 3 (LncRNA MEG3), miR-23a, and apoptosis signal-regulating kinase 1 (ASK1) are factors associated with autophagy. However, whether these factors can regulate autophagy in cumulus cells (CCs) of yak is unclear. Here, miR-23a overexpression upregulated the LC3-II/LC3-I ratio and Beclin1 abundance while reducing p62 accumulation (p < 0.05). The monodansylcadaverine assay exhibited a marked increase in punctate green fluorescence, and the GFP-LC3B displayed increased yellow fluorescence (p < 0.05). The opposite effect was observed for miR-23a inhibitors. Furthermore, miR-23a overexpression downregulated the abundance of ASK1 mRNA and total ASK1 protein (t-ASK1), whereas miR-23a inhibitors up-regulated them (p < 0.05). The effects of miR-23a overexpression on ASK1 phosphorylated protein at serine 845 (P-845), total JNK (c-Jun N-terminal kinase) (t-JNK) and the JNK phosphorylated protein (p-JNK) were similar to those of t-ASK1 but elicited the opposite effect on ASK1 phosphorylated protein at serine 967 (P-967) (p < 0.05). We further demonstrated that ASK1 expression can be silenced by small-interfering RNA (siRNA), which had no significant effect on t-JNK abundance (p > 0.05) but significantly suppressed the p-JNK expression (p < 0.05). Silencing ASK1 significantly improved Beclin1 abundance and the LC3-II/LC3-I ratio, but decreased p62 abundance (p < 0.05). An increase in yellow GFP-LC3B puncta and green MDC staining puncta were observed (p < 0.05). Overexpression of LncRNA MEG3 significantly increased the expression of t-ASK1, P-845, and JNK and decreased the abundance of P-967 and miR-23a (p < 0.05). In addition, miR-23a upregulation reduced the number of the TUNEL-positive cells, and the addition of 8 mM 3-methyladenine (3-MA) reversed this downregulation (p < 0.05). Similar trends were observed for the Bax/Bcl2 ratio and cleaved-caspase3 abundance. In summary, miR-23a promotes autophagy by inhibiting ASK1 abundance, which reduces apoptosis of yak CCs. This effect can be inhibited by LncRNA MEG3, which has implications for decreasing abnormal Graafian follicular atresia and maintaining development.
Increasing evidence shows that the abnormal long non-coding RNAs (lncRNAs) expression is closely related to ischemia-reperfusion injury (I/R) progression. Studies have previously described that lncRNA MEG3 regulates pyroptosis in various organs I/R. Nevertheless, the related mechanisms of MEG3 in testicular I/R has not been clarified. The aim of this research is to unravel underlying mechanisms of the regulation of pyroptosis mediated by MEG3 during testicular I/R. We have established a testicular torsion/detorsion (T/D) model and an oxygen-glucose deprivation/reperfusion (OGD/R)-treated spermatogenic cell model. Testicular ischemic injury was assessed by H&E staining. Western blotting, quantitative real-time PCR, MDA, and SOD tests and immunohistochemistry measured the expression of MEG3 and related proteins and the level of ROS production in testicular tissues. Quantitative real-time PCR and western blotting determined the relative expression of MEG3, miR-29a, and relevant proteins in GC-1. Cell viability and cytotoxicity were measured by CCK-8 and LDH assays. Secretion and expression levels of inflammatory proteins were determined by ELISA, immunofluorescence and western blotting. The interaction among MEG3, miR-29a, and PTEN was validated through a dual luciferase reporter assay and Ago2-RIP. In this research, we identified that MEG3 was upregulated in animal specimens and GC-1. In loss of function or gain of function assays, we verified that MEG3 could promote pyroptosis. Furthermore, we found that MEG3 negatively regulated miR-29a expression at the posttranscriptional level and promoted PTEN expression, and further promoted pyroptosis. Therefore, we explored the interaction among MEG3, miR-29a and PTEN and found that MEG3 directly targeted miR-29a, and miR-29a targeted PTEN. Overexpression of miR-29a effectively eliminated the upregulation of PTEN induced by MEG3, indicating that MEG3 regulates PTEN expression by targeting miR-29a. In summary, our research indicates that MEG3 contributes to pyroptosis by regulating miR-29a and PTEN during testicular I/R, indicating that MEG3 may be a potential therapeutic target in testicular torsion.
Hepatic ischemia and reperfusion injury is characterized by hepatocyte apoptosis, impaired autophagy, and oxidative stress. Fenofibrate, a commonly used antilipidemic drug, has been verified to exert hepatic protective effects in other cells and animal models. The purpose of this study was to identify the function of fenofibrate on mouse hepatic IR injury and discuss the possible mechanisms. A segmental (70%) hepatic warm ischemia model was established in Balb/c mice. Serum and liver tissue samples were collected for detecting pathological changes at 2, 8, and 24 h after reperfusion, while fenofibrate (50 mg/kg, 100 mg/kg) was injected intraperitoneally 1 hour prior to surgery. Compared to the IR group, pretreatment of FF could reduce the inflammatory response and inhibit apoptosis and autophagy. Furthermore, fenofibrate can activate PPAR-α, which is associated with the phosphorylation of AMPK.
Objective: To evaluate the effect of p-coumaric acid against adriamycin-induced hepatotoxicity in rats.
Methods: The rats were divided into 4 groups. The control group received solvent; the p-coumaric acid group was treated with 100 mg/kg of p-coumaric acid orally for five consecutive days; the adriamycin group was administered with a single dose of adriamycin (15 mg/kg, i.p.), and the p-coumaric acid + adriamycin group was given p-coumaric acid five days before adriamycin administration. Twenty-four hours after the last administration, blood samples were collected for biochemical analysis, and liver tissues were removed for histopathological and immunohistochemistrical studies. Moreover, the levels of tissue lipid peroxidation and enzyme activities of glutathione peroxidase, superoxide dismutase, and catalase in liver tissue were measured.
Results: Treatment with p-coumaric acid protected the liver from the toxicity of adriamycin by attenuating the increase in alkaline phosphatase, alanine transaminase, aspartate transaminase, total bilirubin, total cholesterol, triglyceride, and low-density lipoprotein cholesterol and lessening the decrease in high-density lipoprotein cholesterol and albumin. p-Coumaric acid also raised the levels of glutathione peroxidase, superoxide dismutase, and catalase, as well as decreased lipid peroxidation in liver tissue and hepatic IL- 1β expression. Additionally, histopathological study confirmed the protective effect of p-coumaric acid against liver damage.
Conclusions: p-Coumaric acid can alleviate adriamycin-induced hepatotoxicity.
Urban particulate matter (UPM) is recognized as a grave public health problem worldwide. Although a few studies have linked UPM to ocular surface diseases, few studies have reported on retinal dysfunction. Thus, the aim of the present study was to evaluate the influence of UPM on the retina and identify the main mechanism of UPM toxicity. In this study, we found that UPM significantly induced cytotoxicity with morphological changes in ARPE-19 human retinal pigment epithelial (RPE) cells and increased necrosis and autophagy but not apoptosis. Furthermore, UPM significantly increased G2/M arrest and simultaneously induced alterations in cell cycle regulators. In addition, DNA damage and mitochondrial dysfunction were remarkably enhanced by UPM. However, the pretreatment with the potent reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) effectively suppressed UPM-mediated cytotoxicity, necrosis, autophagy, and cell cycle arrest. Moreover, NAC markedly restored UPM-induced DNA damage and mitochondrial dysfunction. Meanwhile, UPM increased the expression of mitophagy-regulated proteins, but NAC had no effect on mitophagy. Taken together, although further studies are needed to identify the role of mitophagy in UPM-induced RPE injury, the present study provides the first evidence that ROS-mediated cellular damage through necrosis and autophagy is one of the mechanisms of UPM-induced retinal disorders.
Exposure to ambient air pollution is a well-established determinant of health and disease. The Lancet Commission on pollution and health concludes that air pollution is the leading environmental cause of global disease and premature death. Indeed, there is a growing body of evidence that links air pollution not only to adverse cardiorespiratory effects but also to increased risk of cerebrovascular and neuropsychiatric disorders. Despite being a relatively new area of investigation, overall, there is mounting recent evidence showing that exposure to multiple air pollutants, in particular to fine particles, may affect the central nervous system (CNS) and brain health, thereby contributing to increased risk of stroke, dementia, Parkinson's disease, cognitive dysfunction, neurodevelopmental disorders, depression and other related conditions. The underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests inflammation and oxidative stress to be crucial factors in the pathogenesis of air pollution-induced disorders, driven by the enhanced production of proinflammatory mediators and reactive oxygen species in response to exposure to various air pollutants. From a public health perspective, mitigation measures are urgent to reduce the burden of disease and premature mortality from ambient air pollution.
Background: Air pollution has been shown to be associated with blood lipid levels. However, studies on long-term ambient particulate matter with aerodynamic diameter ≤1 μm (PM 1) exposure in high-exposure areas are still limited. This study aimed to explore the associations among long-term PM 1 exposure, blood lipids and dyslipidemias. Methods: Baseline data of The Henan Rural Cohort study was used in present study, including a total of 39,259 participants aged from 18 to 79 years. Daily levels of PM 1 were estimated by a spatiotemporal model using ground-level measurements of PM 1 , satellite remote sensing data and other predictors, according to participants' home addresses. Individual exposure to PM 1 was the 3-year average before baseline investigation. Linear regression and logistic regression models were applied to examine the associations among PM 1 , blood lipids ((total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)), and prevalence of dyslipidemias. Results: The 3-year concentration of PM 1 was 55.7 ± 2.1 μg/m 3. Each 1 μg/m 3 increment of PM 1 was associated with an increase of 0.21% (95% confidence interval (CI): 0.11%-0.31%) in TC and 0.75% (95% CI: 0.61%-0.90%) in LDL-C, while decrease of 2.68% (95% CI: 2.43%-2.93%) in TG and 0.47% (95% CI: 0.35%-0.59%) in HDL-C. Each 1 μg/m 3 increase in PM 1 was associated with 6% (95% CI: 4%-8%), 3% (95% CI: 2%-5%) and 5% (95% CI: 3%-7%) higher risks of hypercholesterolemia, hyperbetalipoproteinemia and hy-poalphalipoproteinemia. Sex, age and BMI statistically modified the associations between PM 1 with blood lipid levels and dyslipidemias. Conclusions: Higher PM 1 exposure was associated with adverse changes of blood lipid levels and dyslipidemias. Males, older and overweight participants were susceptive to the adverse effects of PM 1 .
Background
Air pollution has been shown to be associated with blood lipid levels. However, studies on long-term ambient particulate matter with aerodynamic diameter ≤1 μm (PM1) exposure in high-exposure areas are still limited. This study aimed to explore the associations among long-term PM1 exposure, blood lipids and dyslipidemias.
Methods
Baseline data of The Henan Rural Cohort study was used in present study, including a total of 39,259 participants aged from 18 to 79 years. Daily levels of PM1 were estimated by a spatiotemporal model using ground-level measurements of PM1, satellite remote sensing data and other predictors, according to participants' home addresses. Individual exposure to PM1 was the 3-year average before baseline investigation. Linear regression and logistic regression models were applied to examine the associations among PM1, blood lipids ((total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C)), and prevalence of dyslipidemias.
Results
The 3-year concentration of PM1 was 55.7 ± 2.1 μg/m³. Each 1 μg/m³ increment of PM1 was associated with an increase of 0.21% (95% confidence interval (CI): 0.11%–0.31%) in TC and 0.75% (95% CI: 0.61%–0.90%) in LDL-C, while decrease of 2.68% (95% CI: 2.43%–2.93%) in TG and 0.47% (95% CI: 0.35%–0.59%) in HDL-C. Each 1 μg/m³ increase in PM1 was associated with 6% (95% CI: 4%–8%), 3% (95% CI: 2%–5%) and 5% (95% CI: 3%–7%) higher risks of hypercholesterolemia, hyperbetalipoproteinemia and hypoalphalipoproteinemia. Sex, age and BMI statistically modified the associations between PM1 with blood lipid levels and dyslipidemias.
Conclusions
Higher PM1 exposure was associated with adverse changes of blood lipid levels and dyslipidemias. Males, older and overweight participants were susceptive to the adverse effects of PM1.
Dietary phenols are antioxidants with diverse physiological functions that are beneficial for human health. The objective of this research work was to investigate antioxidant activity of p-coumaric acid (p-CA) using four in vitro methods, the protective effects against oxidative stress in PC12 cells, and hypolipidemic effects on High fat-diet (HFD) mice model. The p-CA exhibited moderate antioxidant activity in the selected in vitro assay. The highest chelating activity of p-CA at 50 μg/mL was found to be 52.22%. Pretreatment with p-CA significantly enhanced cell viability of PC12 cell and suppressed AAPH-induced intracellular ROS generation and AAPH-induced LDH release. The hypolipidemic effects of p-CA (100 mg/kg BW) was directly linked to the increased expression of nuclear factor erythroid 2-related factor (Nrf2) by 2.0-fold, Glutathione peroxidase (Gpx) by 3.8-fold, Superoxide dismutase (SOD-1) by 1.6-fold, Heme oxygenase (HO-1) by 1.72-fold and NAD(P)H Quinone Dehydrogenase 1 (NQO-1) by 1.5-fold compared with HFD group. In addition to these effects, p-CA decreased total cholesterol and atherosclerosis index levels, and increased catalase (CAT) level in serum, total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) levels in liver as compared HFD group. Administration of p-CA also promoted the recovery of hyperlipidemia steatohepatitis in mice by ameliorating lipid peroxidation. These results suggested that p-CA is a potent antioxidant with potential therapeutic efficacy for treating hyperlipidemia symptoms.
Electrophiles and reactive oxygen species (ROS) play a major role in modulating cellular defense mechanisms as well as physiological functions, and intracellular signaling. However, excessive ROS generation (endogenous and exogenous) can create a state of redox imbalance leading to cellular and tissue damage (Ma and He, 2012) [1]. A growing body of research data strongly suggests that imbalanced ROS and electrophile overproduction are among the major prodromal factors in the onset and progression of several cerebrovascular and neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), stroke, Alzheimer's disease (AD), Parkinson's disease (PD), and aging (Ma and He, 2012; Ramsey et al., 2017; Salminen et al., 2012; Sandberg et al., 2014; Sarlette et al., 2008; Tanji et al., 2013) [1–6]. Cells offset oxidative stress by the action of housekeeping antioxidative enzymes (such as superoxide dismutase, catalase, glutathione peroxidase) as well direct and indirect antioxidants (Dinkova-Kostova and Talalay, 2010) [7]. The DNA sequence responsible for modulating the antioxidative and cytoprotective responses of the cells has been identified as the antioxidant response element (ARE), while the nuclear factor erythroid 2-related factor (NRF2) is the major regulator of the xenobiotic-activated receptor (XAR) responsible for activating the ARE-pathway, thus defined as the NRF2-ARE system (Ma and He, 2012) [1]. In addition, the interplay between the NRF2-ARE system and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-ĸB, a protein complex that controls cytokine production and cell survival), has been further investigated in relation to neurodegenerative and neuroinflammatory disorders. On these premises, we provide a review analysis of current understanding of the NRF2-NF-ĸB interplay, their specific role in major CNS disorders, and consequent therapeutic implication for the treatment of neurodegenerative and cerebrovascular diseases.
Air pollution is a complex mixture of gaseous and particulate components, each of which has detrimental effects on human health. While the composition of air pollution varies greatly depending on the source, studies from across the world have consistently shown that air pollution is an important modifiable risk factor for significantly increased morbidity and mortality. Moreover, clinical studies have generally shown a greater impact of particulate matter (PM) air pollution on health than the gaseous components. PM has wide-ranging deleterious effects on human health, particularly on the cardiovascular system. Both acute and chronic exposure to PM air pollution is associated with increased risk of death from cardiovascular diseases including ischemic heart disease, heart failure, and ischemic/thrombotic stroke. Particulate matter has also been shown to be an important endocrine disrupter, contributing to the development of metabolic diseases such as obesity and diabetes mellitus, which themselves are risk factors for cardiovascular disease. While the epidemiological evidence for the deleterious effects of PM air pollution on health is increasingly accepted, newer studies are shedding light on the mechanisms by which PM exerts its toxic effects. A greater understanding of how PM exerts toxic effects on human health is required in order to prevent and minimize the deleterious health effects of this ubiquitous environmental hazard. Air pollution is a growing public health problem and mortality due to air pollution is expected to double by 2050. Here, we review the epidemiological evidence for the cardiovascular effects of PM exposure and discuss current understanding about the biological mechanisms, by which PM exerts toxic effects on cardiovascular system to induce cardiovascular disease.
Air pollution is a very critical issue worldwide, particularly in developing countries. Particulate matter (PM) is a type of air pollution that comprises a heterogeneous mixture of different particle sizes and chemical compositions. There are various sources of fine PM (PM2.5), and the components may also have different effects on people. The pathogenesis of PM2.5 in several diseases remains to be clarified. There is a long history of epidemiological research on PM2.5 in several diseases. Numerous studies show that PM2.5 can induce a variety of chronic diseases, such as respiratory system damage, cardiovascular dysfunction, and diabetes mellitus. However, the epidemiological evidence associated with potential mechanisms in the progression of diseases need to be proved precisely through in vitro and in vivo investigations. Suggested mechanisms of PM2.5 that lead to adverse effects and chronic diseases include increasing oxidative stress, inflammatory responses, and genotoxicity. The aim of this review is to provide a brief overview of in vitro and in vivo experimental studies of PM2.5 in the progression of various diseases from the last decade. The summarized research results could provide clear information about the mechanisms and progression of PM2.5-induced disease.
Purpose of review:
Air pollution significantly affects health, causing up to 7 million premature deaths annually with an even larger number of hospitalizations and days of sick leave. Climate change could alter the dispersion of primary pollutants, particularly particulate matter, and intensify the formation of secondary pollutants, such as near-surface ozone. The purpose of the review is to evaluate the recent evidence on the impacts of climate change on air pollution and air pollution-related health impacts and identify knowledge gaps for future research.
Recent findings:
Several studies modelled future ozone and particulate matter concentrations and calculated the resulting health impacts under different climate scenarios. Due to climate change, ozone- and fine particle-related mortalities are expected to increase in most studies; however, results differ by region, assumed climate change scenario and other factors such as population and background emissions. This review explores the relationships between climate change, air pollution and air pollution-related health impacts. The results highly depend on the climate change scenario used and on projections of future air pollution emissions, with relatively high uncertainty. Studies primarily focused on mortality; projections on the effects on morbidity are needed.
Ambient air particulate matter (PM) represents a class of heterogeneous substances that form one component of air pollution. Oxidative stress has been implicated as an important action mechanism for PM on the human organism. Oxidative damage induced by reactive oxygen species (ROS) may affect any cellular macromolecule. The aim of our study was to investigate the impact of air pollution on oxidative DNA damage [8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)] and lipid peroxidation [15-F2t-isoprostane (15-F2t-IsoP)] in the urine and blood from mothers and newborns from two localities with different levels of air pollution: Ceske Budejovice (CB), a locality with a clean air, and Karvina, a locality with high air pollution. The samples from normal deliveries (38-41 week+) of nonsmoking mothers and their newborns were collected in the summer and winter seasons. Higher PM2.5 concentrations were found in Karvina than in CB in the summer 2013 (mean±SD: 20.41±6.28 vs. 9.45±3.62μg/m(3), P<0.001), and in the winter 2014 (mean±SD: 53.67±19.76 vs. 27.96±12.34μg/m(3), P<0.001). We observed significant differences in 15-F2t-IsoP levels between the summer and winter seasons in Karvina for newborns (mean±SD: 64.24±26.75 vs. 104.26±38.18pg/ml plasma, respectively) (P<0.001). Levels of 8-oxodG differed only in the winter season between localities, they were significantly higher (P<0.001) in newborns from Karvina in comparison with CB (mean±SD: 5.70±2.94 vs. 4.23±1.51 nmol/mmol creatinine, respectively). The results of multivariate regression analysis in newborns from Karvina showed PM2.5 concentrations to be a significant predictor for 8-oxodG excretion, PM2.5 and B[a]P (benzo[a]pyrene) concentrations to be a significant predictor for 15-F2t-IsoP levels. The results of multivariate regression analysis in mothers showed PM2.5 concentrations to be a significant predictor of 8-oxodG levels.
Long noncoding RNAs (LncRNAs) have been believed to be the major transcripts in various tissues and organs, and may play important roles in regulation of many biological processes. The current study determined the LncRNA profile in mouse plasma after liver ischemia/reperfusion injury (IRI) using microarray technology. Microarray assays revealed that 64 LncRNAs were upregulated, and 244 LncRNAs were downregulated in the plasma of liver IRI mouse. Among these dysregulated plasma LncRNAs, 59-61% were intergenic, 22-25% were antisense overlap, 8-12% were sense overlap and 6-7% were bidirectional. Ten dysregulated plasma LncRNAs were validated by quantitative PCR assays, confirming the accuracy of microarray analysis result. Comparison analysis between dysregulated plasma and liver LncRNA profile after liver IRI revealed that among the 308 dysregulated plasma LncRNAs, 245 LncRNAs were present in the liver, but remained unchanged. In contrast, among the 98 dysregulated liver LncRNAs after IRI, only 19 were present in the plasma, but remained unchanged. LncRNA AK139328 had been previously reported to be upregulated in the liver after IRI, and silencing of hepatic AK139328 ameliorated liver IRI. Both microarray and RT-PCR analyses failed to detect the presence of AK139328 in mouse plasma. In summary, the current study compared the difference between dysregulated LncRNA profile in mouse plasma and liver after liver IRI, and suggested that a group of dysregulated plasma LncRNAs have the potential of becoming novel biomarkers for evaluation of ischemic liver injury.
Air pollution is associated with cardiovascular disease, and systemic inflammation may mediate this effect. We assessed associations between long- and short-term concentrations of air pollution and markers of inflammation, coagulation, and endothelial activation.
We studied participants from the Multi-Ethnic Study of Atherosclerosis from 2000 to 2012 with repeat measures of serum C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, D-dimer, soluble E-selectin, and soluble Intercellular Adhesion Molecule-1. Annual average concentrations of ambient fine particulate matter (PM2.5), individual-level ambient PM2.5 (integrating indoor concentrations and time-location data), oxides of nitrogen (NOx), nitrogen dioxide (NO2), and black carbon were evaluated. Short-term concentrations of PM2.5 reflected the day of blood draw, day prior, and averages of prior 2-, 3-, 4-, and 5-day periods. Random-effects models were used for long-term exposures and fixed effects for short-term exposures. The sample size was between 9,000 and 10,000 observations for CRP, IL-6, fibrinogen, and D-dimer; approximately 2,100 for E-selectin; and 3,300 for soluble Intercellular Adhesion Molecule-1.
After controlling for confounders, 5 µg/m increase in long-term ambient PM2.5 was associated with 6% higher IL-6 (95% confidence interval = 2%, 9%), and 40 parts per billion increase in long-term NOx was associated with 7% (95% confidence interval = 2%, 13%) higher level of D-dimer. PM2.5 measured at day of blood draw was associated with CRP, fibrinogen, and E-selectin. There were no other positive associations between blood markers and short- or long-term air pollution.
These data are consistent with the hypothesis that long-term exposure to air pollution is related to some markers of inflammation and fibrinolysis.
Long non-coding RNAs (lncRNAs) are non-protein coding transcripts longer than 200 nucleotides. The post-transcriptional regulation is influenced by these lncRNAs by interfering with the microRNA pathways, involving in diverse cellular processes. The regulation of gene expression by lncRNAs at the epigenetic level, transcriptional and post-transcriptional level have been well known and widely studied. Recent recognition that lncRNAs make effects in many biological and pathological processes such as stem cell pluripotency, neurogenesis, oncogenesis and etc. This review will focus on the functional roles of lncRNAs in epigenetics and related research progress will be summarized.
Recent episodes of severe air pollution in eastern Asia have been reported in the scientific literature and news media. Therefore, there is growing concern about the systemic effects of air pollution on human health. Along with the other well-known harmful effects of air pollution, recently, several animal models have provided strong evidence that air pollutants can induce liver toxicity and act to accelerate liver inflammation and steatosis. This review briefly describes examples where exposure to air pollutants was involved in liver toxicity, focusing on how particulate matter (PM) or carbon black (CB) may be translocated from lung to liver and what liver diseases are closely associated with these air pollutants.
Liver injury or dysfunction is considered as a serious health problem. The available synthetic drugs to treat liver disorders are expensive and cause further damage. Hence, hepatoprotective effects of some herbal drugs have been investigated, and one of the methods to choose herbs in order to study their biological effects is to search in ancient medical texts. Avicenna who is known as the prince of physicians had collected and classified Greek, Persian and Islamic medicine in the best possible way in the book of Canon in Arabic.
Avicenna's book of The Canon of Medicine was reviewed to find the hepatoprotective herbs.
Three different versions of the Canon were prepared and utilized. To find scientific names of plants we took advantage of three botany references. All of the herbs were investigated on the basis of scientific data from hepatoprotective effects point of view. The searched term was "hepatoprotective" without narrowing and limiting. The searched databases included Cochrane library, Web of science, SID, Irandoc and IranMedex.
18 plants were found. 85% of the presented species, genus or families of plants were reported to have hepatoprotective properties and in the remaining 15% there were no reports of hepatoprotective effect. Flowers and fruits were the most used part of the plants. Most of the plants had simultaneous protective effects on multiple organs but the protective effect on the liver was mostly accompanied by protective effect on the stomach (83%). The average temperament of these herbs is "hot" in the 2nd phase of the 2nd grade, and "dry" in the 3rd phase of the 2nd grade. Hepatoprotective herbs mostly prescribed as a part of hepatoprotective compound drugs formula or other formula for liver diseases are Crocus sativus, Pistacia lentiscus, and Cinnamomum spp.
Maybe there is common mechanism for protecting both liver and stomach. Aquilaria agallocha, Aquilaria malaccensis, and Ruscus aculeatus whose hepatoprotective effects have not yet been reported are considered as good candidates for future investigations. Given that Crocus sativus, and Cinnamomum spp are used as flavors in most countries, they will be introduced for more investigation in order to produce hepatoprotective drugs.
Widespread occupational exposure to carbon black nanoparticles (CBNPs) raises concerns over their safety. CBNPs are genotoxic in vitro but less is known about their genotoxicity in various organs in vivo.
We investigated inflammatory and acute phase responses, DNA strand breaks (SB) and oxidatively damaged DNA in C57BL/6 mice 1, 3 and 28 days after a single instillation of 0.018, 0.054 or 0.162 mg Printex 90 CBNPs, alongside sham controls. Bronchoalveolar lavage (BAL) fluid was analyzed for cellular composition. SB in BAL cells, whole lung and liver were assessed using the alkaline comet assay. Formamidopyrimidine DNA glycosylase (FPG) sensitive sites were assessed as an indicator of oxidatively damaged DNA. Pulmonary and hepatic acute phase response was evaluated by Saa3 mRNA real-time quantitative PCR.
Inflammation was strongest 1 and 3 days post-exposure, and remained elevated for the two highest doses (i.e., 0.054 and 0.162 mg) 28 days post-exposure (P < 0.001). SB were detected in lung at all doses on post-exposure day 1 (P < 0.001) and remained elevated at the two highest doses until day 28 (P < 0.05). BAL cell DNA SB were elevated relative to controls at least at the highest dose on all post-exposure days (P < 0.05). The level of FPG sensitive sites in lung was increased throughout with significant increases occurring on post-exposure days 1 and 3, in comparison to controls (P < 0.001-0.05). SB in liver were detected on post-exposure days 1 (P < 0.001) and 28 (P < 0.001). Polymorphonuclear (PMN) cell counts in BAL correlated strongly with FPG sensitive sites in lung (r = 0.88, P < 0.001), whereas no such correlation was observed with SB (r = 0.52, P = 0.08). CBNP increased the expression of Saa3 mRNA in lung tissue on day 1 (all doses), 3 (all doses) and 28 (0.054 and 0.162 mg), but not in liver.
Deposition of CBNPs in lung induces inflammatory and genotoxic effects in mouse lung that persist considerably after the initial exposure. Our results demonstrate that CBNPs may cause genotoxicity both in the primary exposed tissue, lung and BAL cells, and in a secondary tissue, the liver.
The effect of diesel exhaust particulate (DEP) exposure on innate, cellular and humoral pulmonary immunity was studied using high-dose, acute-exposure rat, mouse, and cell culture models. DEP consists of a complex mixture of petrochemical-derived organics adsorbed onto elemental carbon particles. DEP is a major component of particulate urban air pollution and a health concern in both urban and occupational environments. The alveolar macrophage is considered a key cellular component in pulmonary innate immunity. DEP and DEP organic extracts have been found to suppress alveolar macrophage function as demonstrated by reduced production of cytokines (interleukin-1 [IL-1], tumor necrosis factor- alpha [TNF- alpha]) and reactive oxygen species (ROS) in response to a variety of agents, including lipopolysaccharide (LPS), interferon- gamma (IFN- gamma), and bacteria. Fractionation of DEP organic extract suggests that this activity was predominately in polyaromatic-containing and more polar (resin) fractions. Organic-stripped DEP did not alter these innate pulmonary immune responses. DEP also depressed pulmonary clearance of Listeria monocytogenes and Bacillus Calmette-Guerin (BCG). The contribution of the organic component of DEP is less well defined with respect to acquired and humoral immunity. Indeed, both DEP and carbon black enhanced humoral immune responses (specific immunoglobulin [Ig] E and IgG) in an ovalbumin-sensitized rat model. It is concluded that both the particulate and adsorbed organics may contribute to DEP-mediated immune alterations.
Background
Diabetic retinopathy (DR) is the serious complication of diabetes, which could lead to blindness. Inflammation and apoptosis are hallmark of DR, but mechanism of their regulation is little known. LncRNA-MEG3 is associated with multiple biological processes including proliferation, apoptosis and inflammation response, and is dramatically decreased in DR. However, the role and underlying mechanism of MEG3 in DR is unclear. This study is aimed to reveal the signaling mechanisms of MEG3 in inflammation and apoptosis of DR.
Methods
ARPE-19 cells were applied for this research. MEG3 was cloned into pcDNA3.1. miR-34a was overexpressed and inhibited by transfecting with mimics and inhibitor, respectively. The expression level was detected by qRT-PCR and western blotting. The targeted regulatory relationship was analyzed by dual luciferase assay. Cytokine secretion, cell viability and apoptosis were detected by ELISA assay, MTT assay and flow cytometry analysis, respectively.
Results
High glucose (HG) inhibited MEG3 and SIRT1 expression and enhanced miR-34a expression. MEG3 could promote SIRT1 expression by targeting miR-34a. MEG3 overexpression and miR-34a knockdown could inhibit HG-induced apoptosis and secretion of inflammation cytokines including IL-1β, IL-6 and TNF-α, but miR-34a overexpression alleviated such effects of MEG3. Furthermore, MEG3 overexpression also inhibited NF-κB signaling pathway and increased Bcl-2/Bax ratio via down-regulating miR-34a.
Conclusion
MEG3 could alleviate HG-inducing apoptosis and inflammation via inhibiting NF-κB signaling pathway by targeting miR-34a/SIRT1 axis. This finding illustrated the function and mechanism of MEG3 in DR, and MEG3 might serve as potential therapeutic target for DR.
Hepatic ischemia/reperfusion (I/R) injury is a pathological process that induces oxidative stress, hepatocyte apoptosis, autophagy, and increased inflammatory cytokines. The process can result in liver injury and dysfunction. Long noncoding RNAs (lncRNAs) are associated with the process of I/R; however, the underlying mechanism is not clear. The present study aimed to investigate the regulatory effect of lncRNA HOTAIR on autophagy during hepatic I/R injury. The expression levels of HOTAIR, LC3, and ATG7 were examined in a hepatic I/R model. We found that HOTAIR and ATG7 expression levels were upregulated and the autophagy level was significantly increased during I/R liver injury. In isolated hepatocytes, knockdown of the expression of HOTAIR attenuated autophagy induced by hydrogen peroxide. Using the bioinformatics database of TargetScan and starbase, we predicted microRNA miRNA-20b-5p might participate in the regulation between HOTAIR and ATG7. The miR-20b-5p level was significantly decreased in I/R livers and was identified to target ATG7 and inhibit its expression. In addition, HOTAIR can function as competing endogenous RNA for miR-20b-5p and attenuates its inhibitory effect on ATG7. Taken together, our findings revealed that HOTAIR regulates autophagy via the miR-20b-5p/ATG7 axis in hepatic I/R injury, which may serve as basis to develop novel therapeutic strategies to treat hepatic I/R injury.
Objective:
To investigate the function of MEG3 in hepatic ischemia-reperfusion (HIR) progress, involving its association with the level of miR-34a during hypoxia-induced hypoxia re-oxygenation (H/R) in vitro.
Methods:
HIR mice model in vivo was established.MEG3 , miR-34a expression, along with Nrf2 mRNA and protein level were detected in tissues and cells. Serum biochemical parameters (ALT and AST) were assessed in vivo. A potential binding region between MEG3 and miR34a was confirmed by luciferase assays. Hepatic cells HL7702 were subjected to hypoxia treatment in vitro for functional studies, including TUNEL-positive cells detection and ROS analysis.
Results:
MEG3, Nrf2 expression was significantly down-regulated in infarction lesion from HIR mice, as opposed to increased miR-34a production, while similar results were also observed in H/R HL7702 cells, while the above effects were reversed by MEG3 over-expression. By using bioinformatics study and RNA pull down combined with luciferase assays, we demonstrated that MEG3 functioned as a competing endogenous RNA (ceRNA) for miR-34a, and there was reciprocal repression between MEG3 and miR-34a in an Argonaute 2-dependent manner. Functional studies demonstrated that MEG3 showed positive regulation on TUNEL-positive cells and ROS level. Further in vivo study confirmed that MEG3 over-expression could improve hepatic function of HIR mice, and markedly decreased the expression of serum ALT and AST.
Conclusion:
MEG3 protected hepatocytes from HIR injury through down-regulating miR-34a expression, which could add our understanding of the molecular mechanisms in HIR injury. This article is protected by copyright. All rights reserved.
General overnutrition but also a diet rich in certain macronutrients, age, insulin resistance and an impaired intestinal barrier function may be critical factors in the development of nonalcoholic fatty liver disease (NAFLD). Here the effect of chronic intake of diets rich in different macronutrients, i.e. fructose and/or fat on liver status in mice, was studied over time. C57BL/6J mice were fed plain water, 30% fructose solution, a high-fat diet or a combination of both for 8 and 16 weeks. Indices of liver damage, toll-like receptor 4 (TLR-4) signaling cascade, macrophage polarization and insulin resistance in the liver and intestinal barrier function were analyzed. Chronic exposure to a diet rich in fructose and/or fat was associated with the development of hepatic steatosis that progressed with time to steatohepatitis in mice fed a combination of macronutrients. The development of NAFLD was also associated with a marked reduction of the mRNA expression of insulin receptor, whereas hepatic expressions of TLR-4, myeloid differentiation primary response gene 88 and markers of M1 polarization of macrophages were induced in comparison to controls. Bacterial endotoxin levels in portal plasma were found to be increased while levels of the tight junction protein occludin and zonula occludens 1 were found to be significantly lower in the duodenum of all treated groups after 8 and 16 weeks. Our data suggest that chronic intake of fructose and/or fat may lead to the development of NAFLD over time and that this is associated with an increased translocation of bacterial endotoxin.
Copyright © 2015. Published by Elsevier Inc.
Small, noncoding microRNAs (miRNAs) regulate diverse biological functions in the liver and increasing evidence suggests that they have a role in liver pathology. This Review summarizes advances in the field of miRNAs in liver diseases, inflammation and cirrhosis. MicroRNA-122, the most abundant miRNA in hepatocytes, has well-defined roles in HCV replication, and data indicate that it also serves as a viable therapeutic target. The role of miR-122 is also emerging in other liver diseases. Ample evidence exists for the important regulatory potential of other miRNAs in conditions associated with liver inflammation related to alcohol use, the metabolic syndrome or autoimmune processes. In addition, a broad array of miRNAs have been associated with the development of liver fibrosis both in animal models and human studies. The significance of the function and cellular distribution of miRNAs in the liver and the potential of miRNAs as a means of communication between cells and organs is discussed as well as the emerging utility of circulating miRNAs as biomarkers of different forms of liver damage and as early markers of disease and progression in hepatocellular carcinoma. Importantly, miRNA modulation in the liver represents a new therapeutic approach in the treatment armamentarium of hepatologists in the future.
The present study evaluated the preventive effects of p-coumaric acid on cardiac hypertrophy and alterations in electrocardiogram, lipids, and lipoproteins in experimentally induced myocardial infarcted rats. Rats were pretreated with p-coumaric acid (8 mg/kg body weight) daily for a period of 7 days and then injected with isoproterenol (100 mg/kg body weight) on 8(th) and 9(th) day to induce myocardial infarction. Myocardial infarction induced by isoproterenol was indicated by increased level of cardiac sensitive marker and elevated ST-segments in the electrocardiogram. Also, the levels/concentrations of serum and heart cholesterol, triglycerides and free fatty acids were increased in myocardial infarcted rats. Isoproterenol also increased the levels of serum low density and very low density lipoprotein cholesterol and decreased the levels of high density lipoprotein cholesterol. It also enhanced the activity of liver 3-hydroxy-3 methyl glutaryl-Coenzyme-A reductase. p-Coumaric acid pretreatment revealed preventive effects on all the biochemical parameters and electrocardiogram studied in myocardial infarcted rats. The in vitro study confirmed the free radical scavenging property of p-coumaric acid. Thus, p-coumaric acid prevented cardiac hypertrophy and alterations in lipids, lipoproteins, and electrocardiogram, by virtue of its antihypertrophic, antilipidemic, and free radical scavenging effects in isoproterenol induced myocardial infarcted rats.
Maternally Expressed Gene 3 (MEG3) is an imprinted gene that encodes a long non-coding RNA (lncRNA) associated with tumorigenesis. Autophagy is activated in cancer cells and contributes to tumor cell survival. However, little is known about whether MEG3 regulates bladder cancer development by controlling autophagy. In the study, we found that MEG3 levels were significantly reduced in bladder cancer tissues compared with normal controls, and autophagy activity was increased in bladder cancer tissues. A significant negative correlation was observed between MEG3 levels and LC3-II (autophagy marker) levels in vivo. We further demonstrated that MEG3 markedly suppressed autophagy activation, whereas MEG3 knockdown activated autophagy in human bladder cancer cell lines. Downregulated expression of MEG3 inhibited cell apoptosis, whereas autophagy inhibition increased MEG3-knockdown cell apoptosis. MEG3 knockdown also increased cell proliferation. More importantly, autophagy inhibition abrogated MEG3 knockdown-induced cell proliferation. These data demonstrated that downregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer.
Hydroxycinnamic acids are the most widely distributed phenolic acids in plants. Broadly speaking, they can be defined as compounds derived from cinnamic acid. They are present at high concentrations in many food products, including fruits, vegetables, tea, cocoa and wine. A diet rich in hydroxycinnamic acids is thought to be associated with beneficial health effects such as a reduced risk of cardiovascular disease. The impact of hydroxycinnamic acids on health depends on their intake and pharmacokinetic properties. This review discusses their chemistry, biosynthesis, natural sources, dietary intake and pharmacokinetic properties.
The long noncoding RNA HOTAIR has been reported as a poor prognostic biomarker in patients with breast cancer. The aim of the present study is to examine the expression pattern of HOTAIR in hepatocellular carcinoma (HCC) and its clinical significance as well as its biological role in tumor progression.
We examined the expression of HOTAIR in 110 HCC samples using real-time reverse transcription-polymerase chain reaction and analyzed its correlation with clinical parameters and prognosis in 60 HCC patients that have undergone liver transplantation (LT). Suppression of HOTAIR using siRNA was performed to explore its roles in tumor progression.
The expression level of HOTAIR in cancer tissues was higher than in adjacent noncancerous tissues. High expression level of HOTAIR was an independent prognostic factor for predicting HCC recurrence in LT patients (P = .001, hazard ratio, 3.564). Furthermore, in patients exceeding the Milan criteria, those with a high expression level of HOTAIR revealed a significantly shorter recurrence-free survival. Moreover, siRNA suppression of HOTAIR in a liver cancer cell line reduced cell viability and cell invasion, sensitized TNF-α induced apoptosis, and increased the chemotherapeutic sensitivity of cancer cells to cisplatin and doxorubicin.
The high expression level of HOTAIR in HCC could be a candidate biomarker for predicting tumor recurrence in HCC patients who have undergone liver transplant therapy and might be a potential therapeutic target.
Diesel exhaust particles (DEP) have been proved to induce serious pulmonary injury, among which lethal pulmonary edema has been assumed to be mediated by vascular endothelial cell damage. In the present study, we investigated the cytotoxic mechanism of DEP on human pulmonary artery endothelial cells focusing on the role of active oxygen species. Endothelial cell viability was assessed by WST-8, a novel tetrazolium salt. Nitric oxide (NO) production was measured by using a new fluorescence indicator, diaminofluorescein-2 (DAF-2). Organic compounds in DEP were extracted by dichloromethane and methanol. DEP-extracts damaged endothelial cells under both subconfluent and confluent conditions. The DEP-extract-induced cytotoxicity was markedly reduced by treatment with SOD, catalase, N-(2-mercaptopropionyl)-glycine (MPG), or ebselen (a selenium-containing compound with glutathione peroxidase-like activity). Thus superoxide, hydrogen peroxide, and other oxygen-derived free radicals are likely to be implicated in DEP-extract-induced endothelial cell damage. Moreover, L-NAME and L-NMA, inhibitors of NO synthase, also attenuated DEP-extract-induced cytotoxicity, while sepiapterin, the precursor of tetrahydrobiopterin (BH(4), a NO synthase cofactor) interestingly enhanced DEP-extract-induced cell damage. These findings suggest that NO is also involved in DEP-extract-mediated cytotoxicity, which was confirmed by direct measurement of NO production. These active oxygen species, including peroxynitrite, may explain the mechanism of endothelial cell damage upon DEP exposure during the early stage.
Isolated alterations of biochemical markers of liver damage in a seemingly healthy patient can present a challenge for the clinician. In this review we provide a guide to interpreting alterations to liver enzyme levels. The functional anatomy of the liver and pathophysiology of liver enzyme alteration are briefly reviewed. Using a schematic approach that classifies enzyme alterations as predominantly hepatocellular or predominantly cholestatic, we review abnormal enzymatic activity within the 2 subgroups, the most common causes of enzyme alteration and suggested initial investigations.
The purpose of this research was to determine whether airborne fine particulate matter (PM(2.5)) could increase levels of lipid peroxidation and alter intracellular redox status in multiple organs of rats. Thirty-two male Wistar rats were randomly divided into the treated groups using PM(2.5) at different dosages (1.5, 7.5, 37.5 mg/kg) and with a control group using saline. Rats were sacrificed 24 h after one-time intratracheal instillation. Then we investigated the activities of Cu, Zn-superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and the levels of glutathione (GSH) and thiobarbituric acid-reactive substances (TBARS) in hearts, livers, spleens, lungs, kidneys, brains, and testicles. It was found that PM(2.5) at dosages of 7.5 and 37.5 mg/kg significantly increased lipid peroxidation levels in the hearts, livers, lungs, and testicles, decreased SOD, CAT, and GPx activities in the lungs, livers, kidneys, and brains, and depleted GSH levels in all the measured organs compared to the control. There were also differences in the changes of antioxidative enzymes activities and lipid peroxidation levels in seven organs. These results led to a conclusion that airborne PM(2.5) was a systemic toxic agent, not only to respiratory and cardiovascular systems. Its toxic effects might be attributed to oxidative damage mediated by prooxidant/antioxidant imbalance or excess free radicals. Further work is required to explain the toxicity role of PM(2.5) on multiple organs of mammals.
Hazardous chemicals escape to the environment by a number of natural and/or anthropogenic activities and may cause adverse effects on human health and the environment. Increased combustion of fossil fuels in the last century is responsible for the progressive change in the atmospheric composition. Air pollutants, such as carbon monoxide (CO), sulfur dioxide (SO(2)), nitrogen oxides (NOx), volatile organic compounds (VOCs), ozone (O(3)), heavy metals, and respirable particulate matter (PM2.5 and PM10), differ in their chemical composition, reaction properties, emission, time of disintegration and ability to diffuse in long or short distances. Air pollution has both acute and chronic effects on human health, affecting a number of different systems and organs. It ranges from minor upper respiratory irritation to chronic respiratory and heart disease, lung cancer, acute respiratory infections in children and chronic bronchitis in adults, aggravating pre-existing heart and lung disease, or asthmatic attacks. In addition, short- and long-term exposures have also been linked with premature mortality and reduced life expectancy. These effects of air pollutants on human health and their mechanism of action are briefly discussed.
Exposure to diesel exhaust particles (DEP) is an environmental and occupational health concern. This review examines the cellular actions of the organic and the particulate components of DEP in the development of various lung diseases. Both the organic and the particulate components cause oxidant lung injury. The particulate component is known to induce alveolar epithelial damage, alter thiol levels in alveolar macrophages (AM) and lymphocytes, and activate AM in the production of reactive oxygen species (ROS) and pro-inflammatory cytokines. The organic component, on the other hand, is shown to generate intracellular ROS, leading to a variety of cellular responses including apoptosis. There are a number of differences between the biological actions exerted by these two components. The organic component is responsible for DEP induction of cytochrome P450 family 1 enzymes that are critical to the polycyclic aromatic hydrocarbons (PAH) and nitro-PAH metabolism in the lung as well as in the liver. The particulate component, on the other hand, causes a sustained down-regulation of CYP2B1 in the rat lung. The significance of this effect on pulmonary metabolism of xenobiotics and endobiotics remains to be seen, but may prove to be an important factor governing the interplay of the pulmonary metabolic and inflammatory systems. Long-term exposures to various particles including DEP, carbon black (CB), TiO2, and washed DEP devoid of the organic content, have been shown to produce similar tumorigenic responses in rodents. There is a lack of correlation between tumor development and DEP chemical-derived DNA adduct formation. But the organic component has been shown to generate ROS that produce 8-hydroxydeoxyguanosine (8-OHdG) in cell culture. The organic, but not the particulate, component of DEP suppresses the production of pro-inflammatory cytokines by AM and the development of Th1 cell-mediated immunity. The mechanism for this effect is not yet clear, but may involve the induction of heme oxygenase-1 (HO-1), a cellular genetic response to oxidative stress. Both the organic and the particulate components of DEP enhance respiratory allergic sensitization. Part of the DEP effects may be due to a depletion of glutathione in lymphocytes. The organic component, which is shown to induce IL-4 and IL-10 productions, may skew the immunity toward Th2 response, whereas the particulate component may stimulate both the Th1 and Th2 responses. In conclusion, the literature shows that the particulate and organic components of DEP exhibit different biological actions but both involve the induction of cellular oxidative stress. Together, these effects inhibit cell-mediated immunity toward infectious agents, exacerbate respiratory allergy, cause DNA damage, and under long-term exposure, induce the development of lung tumors.
Air pollution is associated with significant adverse health effects, including increased cardiovascular morbidity and mortality. Exposure to particulate matter with an aerodynamic diameter of <2.5 microm (PM(2.5)) increases ischemic cardiovascular events and promotes atherosclerosis. Moreover, there is increasing evidence that the smallest pollutant particles pose the greatest danger because of their high content of organic chemicals and prooxidative potential. To test this hypothesis, we compared the proatherogenic effects of ambient particles of <0.18 microm (ultrafine particles) with particles of <2.5 microm in genetically susceptible (apolipoprotein E-deficient) mice. These animals were exposed to concentrated ultrafine particles, concentrated particles of <2.5 microm, or filtered air in a mobile animal facility close to a Los Angeles freeway. Ultrafine particle-exposed mice exhibited significantly larger early atherosclerotic lesions than mice exposed to PM(2.5) or filtered air. Exposure to ultrafine particles also resulted in an inhibition of the antiinflammatory capacity of plasma high-density lipoprotein and greater systemic oxidative stress as evidenced by a significant increase in hepatic malondialdehyde levels and upregulation of Nrf2-regulated antioxidant genes. We conclude that ultrafine particles concentrate the proatherogenic effects of ambient PM and may constitute a significant cardiovascular risk factor.
- Y Du
- X Xu
- M Chu
- Y Guo
- J Wang
Y. Du, X. Xu, M. Chu, Y. Guo, J. Wang, J. Thorac. Dis. 2016, 8(1), 8.
- C.-C Cho
- W.-Y Hsieh
- C.-H Tsai
- C Y Chen
- H F Chang
- C S Lin
C.-C. Cho, W.-Y. Hsieh, C.-H. Tsai, C. Y. Chen, H. F. Chang, C. S. Lin,
Int. J. Environ. Res. Public. Health 2018, 15(7), 1380.
- Z Yang
- L Zhou
- L.-M Wu
- M C Lai
- H Y Xie
- F Zhang
- S S Zheng
Z. Yang, L. Zhou, L.-M. Wu, M. C. Lai, H. Y. Xie, F. Zhang,
S. S. Zheng, Ann. Surg. Oncol. 2011, 18(5), 1243.
- B Szabog
B. SzaboG, Nat. Rev. Gastroenterol. Hepatol. 2013, 10(9), 542.
- B Tang
- N Bao
- G He
- J Wang
B. Tang, N. Bao, G. He, J. Wang, Gene 2019, 686, 56.
- J W Kim
- S Park
- C W Lim
- K Lee
- B Kim
J. W. Kim, S. Park, C. W. Lim, K. Lee, B. Kim, Toxicol. Res. 2014,
30(2), 65.
- M Kampa
- E Castanas
M. Kampa, E. Castanas, Environ. Pollut. 2008, 151(2), 362.
- C Sellmann
- J Priebs
- M Landmann
- C Degen
- A J Engstler
- C J Jin
- S Gärttner
- A Spruss
- O Huber
- I Bergheim
C. Sellmann, J. Priebs, M. Landmann, C. Degen, A. J. Engstler,
C. J. Jin, S. Gärttner, A. Spruss, O. Huber, I. Bergheim, J. Nutr.
Biochem. 2015, 26(11), 1183.
- P D Siegel
- R K Saxena
- Q B Saxena
- J K H Ma
- J Y C Ma
- X J Yin
- V Castranova
- N Al-Humadi
- D M Lewis
P. D. Siegel, R. K. Saxena, Q. B. Saxena, J. K. H. Ma, J. Y. C. Ma,
X. J. Yin, V. Castranova, N. Al-Humadi, D. M. Lewis, J. Toxicol.
Environ. Health Part A 2004, 67(3), 221.
- Y Bai
- A K Suzuki
- M Sagai
- Free Radical
Y. Bai, A. K. Suzuki, M. Sagai, Free Radical. Biol. Med. 2001, 30(5), 555.
- J Y C Ma
- J K H Ma
J. Y. C. Ma, J. K. H. Ma, J. Environ. Sci. Health, Part C. 2002, 20(2), 117.
- X Liu
X. Liu, Z. Meng, Inhalation Toxicol. 2005, 17(9), 467.
- A Ambroz
- V Vlkova
- P Rossner
- A Rossnerova
- V Svecova
- A Milcova
- J Pulkrabova
- J Hajslova
- M Veleminsky
- I Solansky
- R J Sram
A. Ambroz, V. Vlkova, P. Rossner, Jr., A. Rossnerova, V. Svecova,
A. Milcova, J. Pulkrabova, J. Hajslova, M. Veleminsky, I. Solansky,
R. J. Sram, Int. J. Hyg. Environ. Health 2016, 219(6), 545.
- H Shamsi-Baghbanan
- A Sharifiyan
- S Esmaeili
- B Minaei
H. Shamsi-Baghbanan, A. Sharifiyan, S. Esmaeili, B. Minaei, Iran. Red
Crescent Med. J. 2014, 16(1), e12313.
- E Giannini
E. Giannini, Can. Med. Assoc. J. 2005, 172(3), 367.