The influence of atmospheric and cellular H2O2 on ROS concentrations and OH radical production in the lung

Atmospheric pollution is a significant cause of oxidative stress in the human pulmonary system. (1–3) Fine particulate matter (PM_2.5) has been linked to adverse health effects due to the size and composition of particulates. Gas-phase chemical species, such as ozone, have also been considered as significant pollutants posing threat to human health.(3-4) However, other reactive gas-phase species, such as peroxides, have hardly been examined.

The epithelial lining fluid (ELF) is a large interface between the atmosphere and human body.(5) Transition metals enter the ELF through inhalation of PM_2.5 and play a key role in the potential occurrence of health effects. In the presence of transition metals, peroxides such as hydrogen peroxide (H₂O₂) are converted into the highly reactive OH radical through Fenton chemistry. Due to its high reactivity, the OH radical is most likely to cause oxidative stress and Fenton chemistry is probably an important OH source in the lung.(6) High levels in both, peroxide and transition metal concentrations in the ELF, could thus have adverse health outcomes.

We investigate the role of the most abundant atmospheric peroxide, H₂O₂, in the formation of reactive oxygen species (ROS: H₂O₂, OH, O₂^-, HO₂)(5) in the human body using a kinetic multilayer model. We find that, besides ambient concentrations, transport to and from lung cells and the circulatory system affects H₂O₂ levels in the ELF and, accordingly, exhaled breath condensate (EBC). The model predicts levels of H₂O₂ in EBC, lung cellular space, and blood, in agreement with the literature. The H₂O₂ concentration in the ELF, where measurements cannot be conducted easily, can be inferred from the model and used to estimate air pollution-induced ROS production in the human body. We present scenarios of atmospherically relevant conditions of H₂O₂ and PM_2.5 pollution in urban and rural areas and simulate the effect of co-inhalation of H₂O₂ and PM_2.5 on ROS production in the ELF. We discuss the hypothesis whether accumulation of H₂O₂, either by inhalation or in-body transport, may be a prerequisite for PM_2.5 toxicity

 

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6. S. Lelieveld, et al., Hydroxyl Radical Production by Air Pollutants in Epithelial Lining Fluid Governed by Interconversion and Scavenging of Reactive Oxygen Species. Environ. Sci. Technol. 55, 14069-14079 (2021).