Abstract:
Environmental exposure to ambient fine particulate matter (PM2.5) has been associated with adverse health outcomes, partly mediated through oxidative stress and metabolic dysregulation. Polycyclic aromatic hydrocarbons (PAHs), toxic constituents of PM2.5, undergo metabolic activation to generate reactive intermediates that promote oxidative stress and inflammation. However, population-based evidence linking internal PAH exposure to systemic metabolic alterations remains limited, particularly in regions affected by seasonal smoke-haze pollution.This cross-sectional study investigated associations between PM2.5 exposure, urinary metabolomic profiles, and PAH biomarkers among adults residing in regions of contrasting air pollution levels in Thailand. Untargeted proton nuclear magnetic resonance (¹H-NMR)based urinary metabolomics was integrated with biomonitoring of PAH-related urinary features. Participants were recruited from Chiang Mai (high exposure; n = 51) during the seasonal smoke-haze period and from Songkhla (low exposure; n = 52) during the same timeframe. Multivariate and univariate statistical analyses were applied to identify exposure-related metabolic differences.Multivariate analyses demonstrated clear separation of urinary metabolic profiles between exposure groups. Eight endogenous metabolites differed significantly (p < 0.05), indicating coordinated perturbations in pathways related to oxidative stress, inflammation, and vascular function. Metabolites involved in antioxidant and endothelial defense, including L-arginine and L-cystathionine, were reduced in the high-exposure group. Several urinary PAH metabolites were significantly elevated in the high-exposure group, confirming greater internal exposure consistent with regional pollution patterns. Correlation and multiple linear regression analyses identified 5-hydroxyindoleacetic acid (5-HIAA) as the endogenous metabolite most consistently and independently associated with multiple PAH metabolites after false discovery rate correction.Overall, these findings demonstrate that ambient PM2.5 exposure is associated with measurable oxidative stressrelated urinary metabolomic alterations linked to PAH burden. The observed metabolic perturbations provide insight into early biological responses to environmental oxidative stress and may contribute to understanding mechanisms underlying pollution-related cardiometabolic vulnerability.