An ω-3-enriched diet alone does not attenuate CCl4-induced hepatic fibrosis

Exposure to the halogenated hydrocarbon carbon tetrachloride (CCl4) leads to hepatic lipid peroxidation, inflammation and fibrosis. Dietary supplementation of (omega-3 fatty acids has been increasingly advocated as being generally anti-inflammatory, though its effect in models of liver fibrosis is mixed. This raises the question of whether diets high in (omega-3 fatty acids will result in a greater sensitivity or resistance to liver fibrosis as a result of environmental toxicants like CCl4. In this study, we fed CCl4-treated mice a high (omega-3 diet (using a mix of docosahexaenoic acid and eicosapentaenoic acid ethyl esters). We also co-administered an inhibitor of soluble epoxide hydrolase, 1-trifluoromethoxypheny1-3-(1-propionylpiperidin-4-y1) urea (TPPU), which has been shown to boost anti-inflammatory epoxy fatty acids that are produced from both omega-3 and (omega-6 dietary lipids. We showed that soluble epoxide inhibitors reduced CCl4-induced liver fibrosis. Three major results were obtained. First, the (omega-3-enriched diet did not attenuate CCl4-induced liver fibrosis as judged by collagen deposition and collagen mRNA expression. Second, the (omega-3-enriched diet raised hepatic tissue levels of several inflammatory lipoxygenase metabolites and prostaglandin, including PGE2. Third, treatment with TPPU in drinking water in conjunction with the (omega-3-enriched diet resulted in a reduction in liver fibrosis compared to all other groups. Taken together, these results indicate that dietary (omega-3 supplementation alone did not attenuate CCl4-induced liver fibrosis. Additionally, oxylipin signaling molecules may play role in the CCl4-induced liver fibrosis in the high o)-3 diet groups. (C) 2016 Elsevier Inc. All rights reserved.