The Oxidative Potential of Fine Particulate Matter and BiologicalPerturbations in Human Plasma and Saliva Metabolome br

ENVIRONMENTAL SCIENCE & TECHNOLOGY(2022)

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摘要
Particulate oxidative potential may comprise a keyhealth-relevant parameter of particulate matter (PM) toxicity. Toidentify biological perturbations associated with particulateoxidative potential and examine the underlying molecularmechanisms, we recruited 54 participants from two dormitoriesnear and far from a congested highway in Atlanta, GA. Fineparticulate matter oxidative potential ("FPMOP") levels at thedormitories were measured using dithiothreitol assay. Plasma andsaliva samples were collected from participants four times forlongitudinal high-resolution metabolic profiling. We conductedmetabolome-wide association studies to identify metabolic signalswith FPMOP. Leukotriene metabolism and galactose metabolismwere top pathways associated with >= 5 FPMOP-related indicatorsin plasma, while vitamin E metabolism and leukotriene metabolism were found associated with most FPMOP indicators in saliva.We observed different patterns of perturbed pathways significantly associated with water-soluble and -insoluble FPMOPs,respectively. We confirmedfive metabolites directly associated with FPMOP, including hypoxanthine, histidine, pyruvate, lactate/glyceraldehyde, and azelaic acid, which were implications of perturbations in acute inflammation, nucleic acid damage and repair,and energy perturbation. The unique metabolic signals were specific to FPMOP, but not PM mass, providing initial indication thatFPMOP might constitute a more sensitive, health-relevant measure for elucidating etiologies related to PM2.5exposures
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关键词
fine particulate matter, oxidative potential, high-resolution metabolomics, dithiothreitol assay, metabolome-wide association study, oxidative stress, inflammation
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