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Induction of Oxidative Stress and Dysfunction of Nitric Oxide-Dependent Vascular Tone Caused by Quinones Contained in Diesel Exhaust Particles
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This article reviews studies of overproduction of reactive oxygen species during reductive activation of quinones contained in diesel exhaust particles. The resulting inhibition of nitric oxide synthase activity causing suppression of vasorelaxation by phenanthraquinone, one of the quinone in diesel exhaust particles, is also reviewed.
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... The toxicology associated with DEP has been attributed to the chemical properties of adsorbed species. For example, compounds found in DEP can induce oxidative stress (Kumagai and Shimojo, 2001; Li et al., 2002), cause vascular dysfunction (Kumagai and Shimojo, 2001), damage DNA (Kumagai et al., 1997), oxidize proximal protein thiols (Kumagai et al., 2002), and induce apoptosis (Hiura et al., 1999). Significantly, these studies utilized DEP extracts and do not consider possible effects associated with the DEP itself. ...
... The toxicology associated with DEP has been attributed to the chemical properties of adsorbed species. For example, compounds found in DEP can induce oxidative stress (Kumagai and Shimojo, 2001; Li et al., 2002), cause vascular dysfunction (Kumagai and Shimojo, 2001), damage DNA (Kumagai et al., 1997), oxidize proximal protein thiols (Kumagai et al., 2002), and induce apoptosis (Hiura et al., 1999). Significantly, these studies utilized DEP extracts and do not consider possible effects associated with the DEP itself. ...
... Among such compounds, quinones are often detected in atmospheric aerosol samples (König et al., 1983;Lewis et al., 1995;Allen et al., 1997;del Rosario Sienra and Rosazza, 2006;, sometimes with concentrations higher than 2 ng m -3 and are suspected to contribute to the toxicity of ambient particles. The toxic effects of quinones are often attributed to their ability to form reactive oxygen species (ROS) (Lemaire and Livingstone, 1997;Kumagai and Shimojo, 2001), but also for their mutagenicity (Chesis et al., 1984;Durant et al., 1996). ...
This work deals with the study of the atmospheric heterogeneous oxidation of polycyclic aromatic compounds (PACs) adsorbed on particles. After the development and the validation of the different analytical procedures, degradation kinetics and oxidation products were investigated for the reactions of NO2, OH and O3 with pyrene, 1-nitropyrene, 1- hydroxypyrene and 9,10-anthraquinone. The measured rate constants allowed to compare the reactivity of the different compounds. The influence of some parameters on the reactivity (nature of particles, PAC concentration...) has also been studied. Finally, the corresponding oxidation products were also measured, and quantified when possible, allowing to a better understanding of the fate of particulate PACs in the atmosphere, through the proposed chemical mechanisms.
... 50 Previous studies have confirmed that fine particle exposure generates reactive oxygen species (ROS). [51][52][53][54][55] The rises in ROS may be attributed to the decrease in PCs consisting of long PUFA chains observed in this study. This observation was consistent with the declines in plasmenylcholines because the vinyl ether bond is susceptible to ROS attack. ...
This study elucidated the underlying pathophysiological changes that occur after chronic ambient fine particulate matter (PM2.5) exposure via a lipidomic approach. Five male Sprague-Dawley rats were continually whole-body exposed to ambient air containing PM2.5 at 16.7 +/- 10.1 [small mu ]g/m3 from the outside of the building for 8 months, whereas a control group (n = 5) inhaled filtered air. Phosphorylcholine-containing lipids were extracted from lung tissue and profiled using ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The phosphatidylcholine (PC) signal features of the two groups were compared using partial least squares discriminant analysis (PLS-DA) and Wilcoxon rank sum tests. The PC profile of the exposure group differed from that of the control group; the R2Y and Q2 were 0.953 and 0.677, respectively, in the PLS-DA model. In the exposure group, a significant 0.66- to 0.80-fold reduction in lyso-PC levels, which may have resulted from repeated inflammation, was
... Among such compounds, quinones are often detected in atmospheric aerosol samples (König et al., 1983;Lewis et al., 1995;Allen et al., 1997;Cho et al., 2004;Shimmo et al., 2004;del Rosario Sienra and Rosazza, 2006;Jakober et al., 2006;Albinet et al., 2007Albinet et al., , 2008; Andreou and Rapsomanikis, 2009;Ringuet et al., 2012a) and are suspected to contribute to the toxicity of ambient particles. Their toxic effects are often attributed to their ability to form reactive oxygen species (ROS) (Lemaire and Livingstone, 1997;Kumagai and Shimojo, 2001), but also for their mutagenicity (Chesis et al., 1984;Durant et al., 1996;Pedersen et al., 2004Pedersen et al., , 2005. Recently, the IARC has classified 9,10-anthraquinone as a group 2B chemical, signifying its carcinogenic probability to humans (IARC, 2012) and highlighting the study of the fate of this compound. ...
... Among such compounds, quinones are often detected in atmospheric aerosol samples (König et al., 1983;Lewis et al., 1995;Allen et al., 1997;del Rosario Sienra and Rosazza, 2006;, sometimes with concentrations higher than 2 ng m -3 and are suspected to contribute to the toxicity of ambient particles. The toxic effects of quinones are often attributed to their ability to form reactive oxygen species (ROS) (Lemaire and Livingstone, 1997;Kumagai and Shimojo, 2001), but also for their mutagenicity (Chesis et al., 1984;Durant et al., 1996). ...
Ce travail a eu pour objectif d'étudier l'oxydation hétérogène de composés aromatiques polycycliques (CAP) adsorbés sur des particules solides, exposés à des oxydants troposphériques. Après adaptation et validation des protocoles analytiques, deux aspects ont été abordés : les cinétiques de dégradation avec O3, NO2 et OH dans un premier temps, puis l'étude des produits d'oxydation formés au cours de ces réactions. Les constantes de vitesse mesurées ont permis de comparer les différences de réactivité entre les composés étudiés (pyrène, 1-nitropyrène, 1-hydroxypyrène, 9,10-anthraquinone). L'influence de différents paramètres sur la réactivité (nature des particules, concentration en HAP...) a aussi été étudiée. Enfin, la détermination des produits d'oxydation et leur quantification, quand cela a été possible, a permis de mieux comprendre le devenir de ces composés particulaires dans l'atmosphère, à travers les mécanismes réactionnels proposés.
... However, the chemicals associated with this toxicity remain uncharacterized. The study indicated that phenanthraquinone (a relatively abundant quinone in DEP) can act as a catalytic oxidizing agent for proximal protein sulfhydryls in addition to its ability to interact with NADPH-cytochrome P450 reductase, leading to the overproduction of reactive oxygen species (5,40). This chemical reactivity indicates that phenanthraquinone may be, at least partially, responsible for DEP-induced oxidative stress. ...
Diesel exhaust particles (DEP) contain quinones that are capable of catalyzing the generation of reactive oxygen species in biological systems, resulting in induction of oxidative stress. In the present study, we explored sulfhydryl oxidation by phenanthraquinone, a component of DEP, using thiol compounds and protein preparations. Phenanthraquinone reacted readily with dithiol compounds such as dithiothreitol (DTT), 2,3-dimercapto-1-propanol (BAL), and 2,3-dimercapto-1-propanesulfonic acid (DMPS), resulting in modification of the thiol groups, whereas minimal reactivities of this quinone with monothiol compounds such as GSH, 2-mercaptoethanol, and N-acetyl-L-cysteine were seen. The modification of DTT dithiol caused by phenanthraquinone proceeded under anaerobic conditions but was accelerated by molecular oxygen. Phenanthraquinone was also capable of modifying thiol groups in pulmonary microsomes from rats and total membrane preparation isolated from bovine aortic endothelial cells (BAEC), but not bovine serum albumin (BSA), which has a Cys34 as a reactive monothiol group. A comparison of the thiol alkylating agent N-ethylmaleimide (NEM) with that of phenanthraquinone indicates that the two mechanisms of thiol modification are distinct. Studies revealed that thiyl radical intermediates and reactive oxygen species were generated during interaction of phenanthraquinone with DTT. From these findings, it is suggested that phenanthraquinone-mediated destruction of protein sulfhydryls appears to involve the oxidation of presumably proximal thiols and the reduction of molecular oxygen.
To validate gene expression profiling of peripheral blood mononuclear cells (PBMCs) as a surrogate for monitoring tissue expression, the present study using RT-PCR based Taqman low density array (TLDA) was initiated to investigate similarities in the mRNA expression of target genes, altered by exposure to diesel exhaust particles (DEPs), in freshly prepared PBMCs and lungs. Adult Wistar rats were treated transtracheally with single dose of 7.5- or 15- or 30mg/kg of DEP and sacrificed 24hours later. Blood and lungs were immediately taken out and processed for RT-PCR. DEP treatment induced a similar pattern of increase in the expression of polycyclic aromatic hydrocarbon responsive cytochrome P450s (CYPs), the phase II enzymes and their associated transcription factors in both, lungs and PBMCs, at all the doses. Similar to that seen in lungs, a dose dependent increase was observed in the expression of genes involved in inflammation such as cytokines, chemokines and adhesion molecules in PBMCs. The expression of various genes involved in DNA repair and apoptosis were also increased in a dose dependent manner in PBMCs and lungs. The present TLDA data indicating similarities in the responsiveness of candidate genes, involved in the toxicity of DEP, in PBMCs with the lungs after exposure to DEP has demonstrated that expression profiles of genes in PBMCs could be used as a surrogate for monitoring the acute toxicity of fine and ultrafine particulate matter present in vehicular emissions.
The surface chemistry, morphology, and size of particles emitted to the atmosphere from diesel engines are described using microFTIR, XPS, SEM, and TEM. Morphologies and chemistries may together define their toxicity. The reaction of the surface of these particles with N2O (or O2) in the absence of catalysts without total DEP oxidation is discussed. This could define the N-states seen on the DEP surfaces. The importance of these findings to the potential for better abatement of such particles from diesel emissions, with an improvement in urban air quality, is discussed.
This work describes the use of well-controlled laboratory flames to produce aerosols of organic carbon (OC) as model particles representative of the OC fraction of combustion-generated particulate matter emissions in fresh exhausts. Water-particle interactions are explored in two specific cases. In the first case, particles are exposed to saturated environments and come into direct contact with liquid water by bubbling flame samples through a column of water. This case is representative of particle-liquid interactions relevant to wet removal routes by particle interception by rain or fog droplets or in biological systems covered with biological fluids composed mostly of water. In the second case, the particles are exposed to sub-saturated vapors with H(2)O concentrations representative of cloud-forming atmospheres. The particles' capacity to serve as atmospheric cloud condensation nuclei (CCN) by rapid growth to droplets was measured and compared to NaCl particles, which are highly soluble particles with well known activation diameters. The results show measureable interactions with water in highly saturated conditions. However, in sub-saturated environments, no growth by water condensation was observed, and fresh emissions of OC nanoparticles are not likely to act as CCN in atmospherically relevant humidity.
Reactions of peroxynitrite with guanine were investigated using density functional theory (B3LYP) employing 6-31G** and AUG-cc-pVDZ basis sets. Single point energy calculations were performed at the MP2/AUG-cc-pVDZ level. Genuineness of the calculated transition states (TS) was tested by visually examining the vibrational modes corresponding to the imaginary vibrational frequencies and applying the criterion that the TS properly connected the reactant and product complexes (PC). Genuineness of all the calculated TS was further ensured by intrinsic reaction coordinate (IRC) calculations. Effects of aqueous media were investigated by solvating all the species involved in the reactions using the polarizable continuum model (PCM). The calculations reveal that the most stable nitro-product complex involving the anion of 8-nitroguanine and a water molecule i.e. 8NO(2)G(-) + H(2)O can be formed according to one reaction mechanism while there are two possible reaction mechanisms for the formation of the oxo-product complex involving 8-oxoguanine and anion of the NO(2) group i.e. 8OG + NO(2)(-). The calculated relative stabilities of the PC, barrier energies of the reactions and the corresponding enthalpy changes suggest that formation of the complex 8OG + NO(2)(-) would be somewhat preferred over that of the complex 8NO(2)G(-) + H(2)O. The possible biological implications of this result are discussed.
The inhibitory effects of diesel exhaust particles (DEP) on superoxide dismutase (SOD) activity were examined in vitro because intratracheal administration of DEP to mice resulted in a suppression of the pulmonary enzyme activity (Sagai et al., Free Radic. Biol. Med. 14:37–47; 1993). Superoxide production, based on the reduction of cytochrome c, was suppressed considerably by the soluble fraction of mouse lung and by purified SOD from bovine erythrocytes, but the suppression was drastically diminished in the presence of methanol-extractable compounds of DEP. Inhibition of SOD by diethyldithiocarbamate was irreversible, but that by 1,2-naphthoquinone (1,2-NQ) and the methanol extract of DEP was removed by dialysis. Inhibition of superoxide mediated cytochrome c reduction by Tiron, a scavenging agent for superoxide, was blocked by the methanol extract and 1,2-NQ in a concentration-dependent manner. In contrast, addition of a large amount of SOD to the reaction mixture resulted in an almost complete disappearance of inhibitory action of not only 1,2-NQ but also the methanol extract. The existence of carbonyl compounds in the DEP was confirmed by thin-layer chromatography (TLC) with 2,4-dinitrophenylhydrazine reagent. Electron spin resonance (ESR) spectra of an incubation mixture of oxidized 1,2-dihydroxynaphthalene in the absence and presence of cytochrome c indicated a reaction between the semiquinone radical of 1,2-NQ and cytochrome c. These results indicate that the apparent reduction in SOD activity by DEP is due to the chemical reaction of superoxide with components like quinones, which reduce levels of superoxide.
In this paper an analytical method is presented for the gas chromatographic determination of aniline, toluidines, monochloroanilines and dichloroanilines and their derivatives in surface water.After a combined alkaline hydrolysis and extraction with iso-octane of the water sample in a Bleidner apparatus, the aromatic amines in the iso-octane extract are brominated and determined with a gas chromatograph equipped with a capillary column with OV-330 and a electron capture detector. The minimum detectable amounts in surface water samples were in the 5-15ng1 range.In the river Rhine aniline, 2-, 3-and 4-monochloroaniline and 3, 4-dichloroaniline were frequently detected. In 1979 mean values respectively 3.0, 0.52, 0.15, 0.22 and 0.40 μg 1.
Nitric oxide is a messenger molecule, mediating the effect of endothelium-derived relaxing factor in blood vessels and the cytotoxic actions of macrophages, and playing a part in neuronal communication in the brain. Cloning of a complementary DNA for brain nitric oxide synthase reveals recognition sites for NADPH, FAD, flavin mononucleotide and calmodulin as well as phosphorylation sites, indicating that the synthase is regulated by many different factors. The only known mammalian enzyme with close homology is cytochrome P-450 reductase.
Background:
Diesel emission particulates (DEP) exert effects on the immune system and act as an adjuvant which enhances allergic inflammation. Animal and human models have delineated the effects of DEP chemicals in enhancing IgE production and promoting T-helper cell-2 (Th2) differentiation. An important primary effect that can explain the DEP-associated humoral and cellular immune responses is the induction of macrophage responses by DEP chemicals. This includes effects on macrophage production of cytokines and chemokines, which may play a role in enhancing allergic inflammation. A potent mechanism in macrophages exposed to DEP chemicals involves the generation of reactive oxygen species (ROS), leading to cellular activation or apoptosis which can be abrogated by antioxidants.
Conclusion:
These findings may establish a role for antioxidant therapy in diminishing the effects of particulate pollutants in asthma.
Evolution has resorted to nitric oxide (NO), a tiny, reactive radical gas, to mediate both servoregulatory and cytotoxic functions. This article reviews how different forms of nitric oxide synthase help confer specificity and diversity on the effects of this remarkable signaling molecule.