Li, N., Xia, T. & Nel, A. E. The role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles. Free Radic. Biol. Med. 44, 1689-1699

Division of NanoMedicine, Department of Medicine, University of California, Los Angeles, CA 90095, USA.
Free Radical Biology and Medicine (Impact Factor: 5.74). 06/2008; 44(9):1689-99. DOI: 10.1016/j.freeradbiomed.2008.01.028
Source: PubMed

ABSTRACT Ambient particulate matter (PM) is an environmental factor that has been associated with increased respiratory morbidity and mortality. The major effect of ambient PM on the pulmonary system is the exacerbation of inflammation, especially in susceptible people. One of the mechanisms by which ambient PM exerts its proinflammatory effects is the generation of oxidative stress by its chemical compounds and metals. Cellular responses to PM-induced oxidative stress include activation of antioxidant defense, inflammation, and toxicity. The proinflammatory effect of PM in the lung is characterized by increased cytokine/chemokine production and adhesion molecule expression. Moreover, there is evidence that ambient PM can act as an adjuvant for allergic sensitization, which raises the possibility that long-term PM exposure may lead to increased prevalence of asthma. In addition to ambient PM, rapid expansion of nanotechnology has introduced the potential that engineered nanoparticles (NP) may also become airborne and may contribute to pulmonary diseases by novel mechanisms that could include oxidant injury. Currently, little is known about the potential adverse health effects of these particles. In this communication, the mechanisms by which particulate pollutants, including ambient PM and engineered NP, exert their adverse effects through the generation of oxidative stress and the impacts of oxidant injury in the respiratory tract will be reviewed. The importance of cellular antioxidant and detoxification pathways in protecting against particle-induced lung damage will also be discussed.

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    • "These " power plants of the cell " also play a critical role in signaling transduction for cell proliferation, apoptosis, calcium storage and metabolism (Clay Montier 2009; Lamson and Plaza 2002; Lee and Wei 2005). Several studies have identified the generation of oxidative stress, by producing reactive oxygen species (ROS), as one of the major mechanisms by which air pollution exert adverse biological effects (Chahine et al. 2007; Li et al. 2008). Mitochondria are the major intracellular sources of ROS, which are generated under normal conditions as by-product of OXPHOS (Hou et al. 2010). "
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    ABSTRACT: Mitochondria are sensitive to environmental toxicants due to their lack of repair capacity. Changes in mitochondrial DNA (mtDNA) content may represent a biologically relevant intermediate outcome in mechanisms linking air pollution and fetal growth restriction. We investigated whether placental mtDNA content is a possible mediator of the association between prenatal NO2 exposure and birth weight. We used data from two independent European cohorts: INMA (n=376; Spain) and ENVIRONAGE (n=550; Belgium). Relative placental mtDNA content was determined as the ratio of two mitochondrial genes (MT-ND1 and MTF3212/R3319) to two control genes (RPLP0 and ACTB). Effect estimates for individual cohorts and the pooled dataset were calculated using multiple linear regression and mixed models. We also performed a mediation analysis. Pooled estimates indicated that a 10µg/m(3) increment in average NO2 exposure during pregnancy was associated with a 4.9% decrease in placental mtDNA content (95% confidence interval (CI): -9.3, -0.3%). and a 48g decrease (95% CI: -87, -9g) in birth weight. However, the association with birth weight was significant for INMA (-66g; 95% CI: -111, -23g) but not for ENVIRONAGE (-20g; 95% CI: -101, 62g). Placental mtDNA content was associated with significantly higher mean birth weight (pooled analysis, IQR increase: 140g; 95% CI: 43, 237g). Mediation analysis estimates, which were derived for the INMA cohort only, suggested that 10% (95% CI: 6.6, 13.0g) of the association between prenatal NO2 and birth weight was mediated by changes in placental mtDNA content. Our results suggest that mtDNA content can be one of the potential mediators of the association between prenatal air pollution exposure and birth weight.
    Environmental Health Perspectives 08/2015; DOI:10.1289/ehp.1408981 · 7.98 Impact Factor
    • "ESR data showed that with the decrease of oxidation degrees, GO possessed more free electrons, stronger oxidative ability and higher facilitative ability on OH production from H 2 O 2 and electron transfer during the reactions. Oxidative stress is a well-recognized toxicological mechanism of various nanoparticles (Sanchez et al., 2011; Lewinski et al., 2008; Li et al., 2008). Considering the indiscriminate ability of OH to induce oxidative damages on various biomolecules, accelerating OH production more efficiently by the less oxidized GOs is doomed to impose stronger oxidative damages on MEFs. "
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    ABSTRACT: The promising broad applications of graphene oxide (GO) derivatives in biomedicine have raised concerns about their safety on biological organisms. However, correlations between the physicochemical properties, especially oxidation degree of GOs and their toxicity, and the underlying mechanisms are not well understood. Herein, we evaluated the cytotoxicity of three GO samples with various oxidation degrees on mouse embryo fibroblasts (MEFs). Three samples can be internalized by MEFs observed via transmission electron microscopy (TEM), and were well tolerant by MEFs at lower doses (below 25μg/ml) but significantly toxic at 50 and 100μg/ml via Cytell Imaging System. More importantly, as the oxidation degree decreased, GO derivatives led to a higher degree of cytotoxicity and apoptosis. Meanwhile, three GOs stimulated dramatic enhancement in reactive oxygen species (ROS) production in MEFs, where the less oxidized GO produced a higher level of ROS, suggesting the major role of oxidative stress in the oxidation-degree dependent toxicity of GOs. Results from electron spin resonance (ESR) spectrometry showed a strong association of the lower oxidation degree of GOs with their stronger indirect oxidative damage through facilitating H2O2 decomposition into OH and higher direct oxidative abilities on cells. The theoretical simulation revealed the key contributions of carboxyl groups and aromatic domain size of nanosheets to varying the energy barrier of H2O2 decomposition reaction. These systematic explorations in the chemical mechanisms unravel the key physicochemical properties that would lead to the diverse toxic profiles of the GO nanosheets with different oxygenation levels, and offer us new clues in the molecular design of carbon nanomaterials for their safe applications in biomedicine. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Toxicology Letters 06/2015; 237(2). DOI:10.1016/j.toxlet.2015.05.021 · 3.26 Impact Factor
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    • "The use of DF confirmed that trace elements play a significant role in ROS formation in vitro. Transition metal ions associated with PM can produce ROS or catalyze the formation of hydroxyl radical from hydrogen peroxide through Fenton and Haber–Weiss reactions (Li et al., 2008). PACs, such as quinone and hydroquinones , can produce the superoxide ion that act as a catalyst for the Fenton and Haber–Weiss reactions (Akhtar et al., 2010; Balakrishna et al., 2009). "
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    ABSTRACT: The health impact of the global African dust event (ADE) phenomenon in the Caribbean has been vaguely investigated. Heavy metals in ADE and non-ADE extracts were evaluated for the formation of reactive oxygen species (ROS) and antioxidant capacity by cells using, deferoxamine mesylate (DF) and N-acetyl-l-cysteine (NAC). Results show that ADE particulate matter 2.5 (PM2.5) induces ROS and stimulates oxidative stress. Pre-treatment with DF reduces ROS in ADE and Non-ADE extracts and in lung cells demonstrating that heavy metals are of utmost importance. Glutathione-S-transferase and Heme Oxygenase 1 mRNA levels are induced with ADE PM and reduced by DF and NAC. ADE extracts induced Nrf2 activity and IL-8 mRNA levels significantly more than Non-ADE. NF-kB activity was not detected in any sample. Trace elements and organic constituents in ADE PM2.5 enrich the local environment load, inducing ROS formation and activating antioxidant-signaling pathways increasing pro-inflammatory mediator expressions in lung cells.
    Environmental Toxicology and Pharmacology 02/2015; 39:845-856. · 2.08 Impact Factor
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