Abstract

Rationale: Exposure to air pollution is associated with adverse health effects through systemic inflammation and oxidative stress. One mechanism of beneficial effects of omega-3 polyunsaturated fatty acids (n-3 FA) is mediated via their inflammation resolution process by generating bioactive lipid mediators known as oxylipins. Objective: This study examined the association between n-3 FA-derived bioactive oxylipins and short-term exposure to ambient air pollution in healthy adults. Methods: Fifteen healthy adults were enrolled into either high or low n-3 groups based on n-3 FA intake and the participants underwent 4-5 blood collections for lipidomic profile of 55 oxylipins. Associations between ambient ozone, nitrogen dioxide (NO 2 ), and fine particulate matter (PM 2.5 ) levels and plasma oxylipins were assessed using mixed-effects models stratified by fatty acids levels. Results: Average concentrations of ozone (40.8±11.1 ppb), NO 2 (5.3±3.8 ppb), and PM 2.5 (10.2±4.1 μg/m 3 ) were below national ambient air quality standards during the study period. Compared to the low n-3 group exposed to ozone and PM 2.5 , high n-3 group had significant reduction in arachidonic acids (AA) derived pro-inflammatory oxylipins produced by lipoxygenase (LOX). For instance, 12 HETE was negatively associated with ozone levels [for an IQR increase in ozone, -58.1% (95% CI:-96.8, -19.4) vs. 14.5% (95% CI:-33, 62)] and PM 2.5 concentrations [for an IQR increase in PM 2.5 , -29.6% (95% CI:-49.1, -10.1) vs. 28.5% (95% CI:-3.8, 60.9)] at lag4 in the high n-3 group while the association was null in the low n-3 group. In contrast, high n-3 group exposed to ozone and PM 2.5 had significant increases in EPA and DHA derived pro-resolving oxylipins produced by LOX and cytochrome p450 (CYP) and soluble epoxide hydrolase (sEH) compared to the low n-3 group. Conclusions: We observed negative associations between short-term ambient air pollutants and pro-inflammatory oxylipins in the high n-3 groups, while the associations between short-term ambient air pollutants and pro-resolving oxylipins were positive in the high n-3 groups, suggesting that n-3 derived lipid mediators may mediate the inflammation resolution process in response to low levels of ambient air pollution in healthy adults.

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