title: Dietary omega-3 polyunsaturated fatty acids attenuate hepatic ischemia/reperfusion injury in rats by modulating toll-like receptor recruitment into lipid rafts.
abstract: OBJECTIVE
  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: Department of Surgery, Eulji General Hospital, Eulji University School of Medicine, Seoul, South Korea.
authors: Kwangsoon
authors: K
authors: Kim
authors: Namhee
authors: N
authors: Jung
authors: Kiho
authors: K
authors: Lee
authors: Jinwoo
authors: J
authors: Choi
authors: Sanghun
authors: S
authors: Kim
authors: Jinhyun
authors: J
authors: Jun
authors: Eunkyung
authors: E
authors: Kim
authors: Donghee
authors: D
authors: Kim
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D019587:Dietary Supplements / Q000009:adverse effects; D004195:Disease Models, Animal; D015536:Down-Regulation; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D043371:Fatty Acids, Omega-6 / Q000009:adverse effects; D005395:Fish Oils / Q000627:therapeutic use; D008099:Liver / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism; D008107:Liver Diseases / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D008297:Male; D021962:Membrane Microdomains / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction; D013024:Soybean Oil / Q000009:adverse effects; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052096:Warm Ischemia / Q000009:adverse effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D005395:Fish Oils; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D013024:Soybean Oil
keywords: HMGB1; Hepatic ischemia/reperfusion injury; I/R; Omega-3 polyunsaturated fatty acids; TLR4; Toll-like receptor 4; high mobility group box 1; ischemia and reperfusion; omega-3 polyunsaturated fatty acids; toll-like receptor 4; ω-3 PUFAs