Hydroxyl Radical Production by Air Pollutants in Epithelial Lining Fluid Governed by Interconversion and Scavenging of Reactive Oxygen Species

Steven Lelieveld,Ulrich Pöschl,Manabu Shiraiwa,Thomas Berkemeier,Ashmi Mishra,Eleni Dovrou,Pascale S J Lakey,Jake Wilson

doi:10.1021/acs.est.1c03875

Abstract

Air pollution is a major risk factor for human health. Chemical reactions in the epithelial lining fluid (ELF) of the human respiratory tract result in the formation of reactive oxygen species (ROS), which can lead to oxidative stress and adverse health effects. We use kinetic modeling to quantify the effects of fine particulate matter (PM2.5), ozone (O3), and nitrogen dioxide (NO2) on ROS formation, interconversion, and reactivity, and discuss different chemical metrics for oxidative stress, such as cumulative production of ROS and hydrogen peroxide (H2O2) to hydroxyl radical (OH) conversion. All three air pollutants produce ROS that accumulate in the ELF as H2O2, which serves as reservoir for radical species. At low PM2.5 concentrations (<10 μg m–3), we find that less than 4% of all produced H2O2 is converted into highly reactive OH, while the rest is intercepted by antioxidants and enzymes that serve as ROS buffering agents. At elevated PM2.5 concentrations (>10 μg m–3), however, Fenton chemistry overwhelms the ROS buffering effect and leads to a tipping point in H2O2 fate, causing a strong nonlinear increase in OH production. This shift in ROS chemistry and the enhanced OH production provide a tentative mechanistic explanation for how the inhalation of PM2.5 induces oxidative stress and adverse health effects.

Highlights

Ambient air pollution is responsible for 4−9 million excess deaths per year.[1−3] Air pollutants can cause and exacerbate ischemic heart disease, cerebrovascular disease, lower respiratory infections, and chronic obstructive pulmonary disease (COPD).[4−6] The air pollutants that most strongly correlate with negative health outcomes are nitrogen dioxide (NO2), ozone (O3), and fine particulate matter with a diameter less than 2.5 μm (PM2.5), with the latter likely contributing more than 80% to the total excess mortality.[7,8]PM2.5 is a complex mixture that can encompass thousands of different chemical constituents, each having distinct properties
At in the epithelial lining fluid (ELF) low PM2.5 as H2O2, which concentrations serves as (
We propose the new chemical metrics of cumulative ROS production rate and H2O2-to-OH conversion fraction to represent the potential of air pollution to induce oxidative stress

Summary

■ INTRODUCTION

Ambient air pollution is responsible for 4−9 million excess deaths per year.[1−3] Air pollutants can cause and exacerbate ischemic heart disease (e.g., myocardial infarction), cerebrovascular disease (e.g., stroke), lower respiratory infections (e.g., pneumonia), and chronic obstructive pulmonary disease (COPD).[4−6] The air pollutants that most strongly correlate with negative health outcomes are nitrogen dioxide (NO2), ozone (O3), and fine particulate matter with a diameter less than 2.5 μm (PM2.5), with the latter likely contributing more than 80% to the total excess mortality.[7,8]. Exposure to O3 has been shown to exacerbate asthma and increase respiratory and circulatory mortality.[8,41,42] It is known to react with alkenes by addition to the C−C double bond, leading to lipid peroxidation and forming a variety of oxidized reaction products, including Criegee intermediates and hydroperoxides.[43−45] while the chemical properties of NO2 and O3 are well understood, the mechanisms behind their health effects and contribution to ROS formation in the ELF, remain unclear. We propose the new chemical metrics of cumulative ROS production rate and H2O2-to-OH conversion fraction to represent the potential of air pollution to induce oxidative stress

■ METHODS

■ RESULTS AND DISCUSSION

■ ACKNOWLEDGMENTS

■ REFERENCES