BACKGROUND & AIMS: Hepatic ischemia/reperfusion (I/R) injury may activate innate immunity through the interaction of toll-like receptor 4 (TLR4) with endogenous ligands. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) exert suppressive effects on innate immunity through various mechanisms. In this study, we investigated the effect of dietary supplementation with ω-3 PUFAs on hepatic I/R in rats. METHODS: Three groups of Wistar male rats were fed a standard diet with water, and fish oil as ω-3 PUFAs, or soybean oil as ω-6 PUFAs for 7 days. Subsequently, the rats underwent normothermic, 60 min, partial liver ischemia followed by 6 h of reperfusion. The activation of TLR4 signaling was evaluated using membrane lipid raft isolation. After the 6 h of reperfusion, histopathologic alterations, serum ALT levels, TLR4-mediated inflammation were assessed by western blotting and immunohistochemical study. RESULTS: The damage of liver from I/R was diminished by dietary fish oil supplementation. Administration of fish oil inhibited TLR4 receptor recruitment into lipid rafts of cell membrane in liver tissues, which is an initial step required for activation of the downstream signaling pathway. Down-regulation of TLR4-mediated signaling reduced NF-κB activation and consequently, improved I/R injury. CONCLUSIONS: Dietary ω-3 PUFAs supplementation attenuated hepatic I/R injury and could be considered as a nutritional therapeutic aimed at ameliorating I/R injury.
BACKGROUND & AIMS:Hepatic ischemia/reperfusion (I/R) injury may activate innate immunity through the interaction of toll-like receptor 4 (TLR4) with endogenous ligands. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) exert suppressive effects on innate immunity through various mechanisms. In this study, we investigated the effect of dietary supplementation with ω-3 PUFAs on hepatic I/R in rats. METHODS: Three groups of Wistar male rats were fed a standard diet with water, and fish oil as ω-3 PUFAs, or soybean oil as ω-6 PUFAs for 7 days. Subsequently, the rats underwent normothermic, 60 min, partial liver ischemia followed by 6 h of reperfusion. The activation of TLR4 signaling was evaluated using membrane lipid raft isolation. After the 6 h of reperfusion, histopathologic alterations, serum ALT levels, TLR4-mediated inflammation were assessed by western blotting and immunohistochemical study. RESULTS: The damage of liver from I/R was diminished by dietary fish oil supplementation. Administration of fish oil inhibited TLR4 receptor recruitment into lipid rafts of cell membrane in liver tissues, which is an initial step required for activation of the downstream signaling pathway. Down-regulation of TLR4-mediated signaling reduced NF-κB activation and consequently, improved I/R injury. CONCLUSIONS: Dietary ω-3 PUFAs supplementation attenuated hepatic I/R injury and could be considered as a nutritional therapeutic aimed at ameliorating I/R injury.
Authors: Gi S Yoon; Sudha Sud; Rahul K Keswani; Jason Baik; Theodore J Standiford; Kathleen A Stringer; Gus R Rosania Journal: Mol Pharm Date: 2015-06-05 Impact factor: 4.939