Metabolic Disorder Enhances Oxidative Stress after Exposure to Aromatic Components of Fine Particulate Matter

Metabolic disorder can exacerbate oxidative damage following exposure to fine particulate matter (PM2.5), but the role of chemical composition in this process remains unclear. This study comprehensively assessed the oxidative stress effect from the synergy of metabolic disorder and the organic components in PM2.5 as well as their molecular features. We high-throughput characterized 942 PM2.5 chemicals from an elderly urban population exposure and found the association between oxidative stress markers of exhaled nitric oxide (eNO) and urinary malondialdehyde (MDA) and 330 and 32 compounds, respec-tively, was enhanced by metabolic disorder. Most of these compounds were aromatics, including PAHs and their functionalized and oxidized products. The integrated explanatory random forest approach incorporating source tracers showed that primary aromatics arising from combustion with a high unsaturation degree, high logKOW, and low volatility were responsible for the increased eNO levels in participants with metabolic disorder, while compounds formed through atmospheric oxidation reactions with high numbers of carbonyl groups and oxygen atoms and relatively low logKOW were associated with elevated MDA in disordered individuals. This study provides the first evidence that metabolic disorder exacerbates oxidative stress after exposure to specific PM2.5 components, which could in turn exacerbate chronic diseases in the elderly population.