Review ArticleThe role of oxidative stress in ambient particulate matter-induced lung diseases and its implications in the toxicity of engineered nanoparticles
Introduction
Increased vehicular traffic and other combustion processes have resulted in a significant increase in ambient particulate matter (PM) over the past two decades. A sudden surge in the level of PM has been linked to increased morbidity and mortality due to cardiorespiratory events, including asthma, chronic obstructive pulmonary disease, and atherosclerosis [1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12]. Both in vitro and in vivo studies of the health effects of ambient PM have identified the generation of oxidative stress as one of the major mechanisms by which air pollution particles exert adverse biological effects. Among particles of different sizes, it has also been established that ultrafine particles (UFP), which have an aerodynamic size of < 100 nm, are potentially the most dangerous due to their small size, large surface area, deep penetration and ability to be retained in the lung, and high content of redox-cycling organic chemicals [3]. In addition, increased use of engineered nanoparticles (NP) in a wide range of industries has introduced a potential new type of inhaled particulate pollutant [13]. Examples include carbon black, TiO2, ZnO, and CeO2 nanoparticles [13]. Currently, little is known about the potential adverse health effects of these particles. Therefore, there is an urgent need to understand the potential impact of inadvertent ambient (UFP) or engineered NP exposure on human health. None of these NP are currently being regulated. In this communication, we will review the mechanisms by which particulate pollutants, including ambient and engineered NP, exert their deleterious effects through an ability to generate reactive oxygen species (ROS) and oxidative stress. We will discuss the role of oxidant injury by ambient and engineered NP in the respiratory tract. We will also discuss the importance of cellular antioxidant and detoxification pathways in protecting against particle-induced lung damage.
Section snippets
The role of oxidative stress in the health effects of particulate pollutants
Several mechanisms have been proposed to explain the adverse health effects of particulate pollutants. These include inflammation, endotoxin effects, stimulation of capsaicin/irritant receptors, autonomic nervous system activity, procoagulant effects, covalent modification of cellular components, and ROS production [3]. Among these, ROS production and the generation of oxidative stress have received the most attention.
Cellular redox homeostasis is carefully maintained by an elaborate
Generation of oxidative stress by ambient particulate pollutants
How is oxidative stress generated by ambient PM? The aerodynamic diameters of ambient particle size vary from 0.005 to 10 μm. Three different types of ambient particles, as defined by size, are characterized in Table 1. Among these, the small size and large surface area of UFP make them carriers for metals and a large number of organic carbon compounds. Many of these PM components are capable of ROS generation, e.g., promotion of Fenton and Haber Weiss chemistry to generate ROS and adverse
The impact of particulate pollutants on asthma
Epidemiological evidence has shown a good correlation between increased ambient PM levels and cardiorespiratory morbidity and mortality [22], [39]. There is growing recognition that susceptible people could be more prone to these adverse health effects and that the protective effect of Tier 1 of the hierarchical oxidative stress model may be helpful in understanding this susceptibility. This is best explained by studies looking at pro-oxidative and proinflammatory PM effects in the lung.
PM is
Potential health effects of engineered nanoparticles
In addition to the inadvertent generation of air pollution particles by the burning of fossil-fuel products, the rapid expansion of nanotechnology may lead to adverse health effects. Nanotechnology broadly refers to the manipulation and manufacture of materials and devices in the size range 1–100 nm. These engineered nanomaterials include nanoparticles, nanospheres, nanotubes, and nanofibers. Whereas engineered NP are in the same size range as ambient UFP, they have their own unique physical
Conclusions
It has been established that there is a close association between exposure to ambient particulate pollutants and increased cardiorespiratory morbidity and mortality. Among the ambient particles, the pulmonary effects of PM10 and PM2.5 have been more extensively studied than the effects of UFP. However, given the physical and chemical properties of UFP, it is very likely that these particles are more dangerous from the perspective of oxidant injury and inflammation than larger sized particles.
Acknowledgments
Funding for this study was provided by U.S. Public Health Service Grants U19 AI070453, RO1 ES10553, and RO1 ES015498, as well as the U.S. EPA STAR award (RD-83241301) to the Southern California Particle Center. This work is also supported by the University of California Lead Campus for Nanotoxicology Training and Research, funded by UC TSR&TP. This work has not been subjected to the EPA for peer and policy review.
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