8 - Supplementation with omega-3 fatty acids potentiates glutathione oxidation in human airway epithelial cells exposed to ozone

Abstract

The health benefits of dietary fish oil consumption have been widely reported. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, two omega-3 fatty acids found in fish oil, have been associated with anti-inflammatory and pro-resolving effects through their metabolism to specialized pro-resolving mediators (SPMs) and displacement of arachidonic acid (AA). However, the 5 and 6 double bonds in EPA and DHA respectively are targets for lipid peroxidation by ozone (O3), a major photochemical pollutant to which millions of Americans are exposed. Products of unsaturated fatty acid peroxidation by O3 have been proposed to mediate functional and inflammatory effects of O3 exposure. Thus, cellular supplementation with omega-3s has the potential to both promote and help resolve inflammation during O3 exposure. To investigate this paradox, we supplemented 16-HBE human airway epithelial cells (HAEC) expressing the fluorogenic glutathione redox potential (EGSH) sensor roGFP overnight with EPA, DHA, the monounsaturated fatty acid oleic acid (OA), or the saturated fatty acid stearic acid (SA). Alterations in EGSH were monitored in real time using live-cell microscopy during exposure to O3. We found that supplementation with EPA and DHA, but not OA or SA, caused a marked potentiation of the O3-induced increases in EGSH, evident as both an accelerated response time and increase in the magnitude of response. Notably, the potentiation of GSH oxidation occurred at O3 concentrations as low as 0.08 ppm, the current National Ambient Air Quality Standard level. These results suggest that membrane fatty acid saturation is a determinant of the oxidative responses to O3 in HAEC. These findings may have implications for dietary recommendations for populations exposed to O3. This abstract does not necessarily reflect EPA policy.