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Abstract Hepatic ischemia reperfusion (IR) injury is common with many medical strategies as liver transplantation and trauma. Aim: Comparing the efficacy and evaluating the possible mechanisms of ischemic preconditioning (IPC), topical hypothermia (TH) and MitoQ treatment in the hepatic IR injury. Method: 67 adult male Wistar albino rats were allocated into five groups: sham control group (n=15), hepatic ischemia reperfusion group (IR) (n=13):where ischemia compromised 70% of the liver for 45 min followed by 90 min of reperfusion, topical hypothermia (TH-IR) group (n=14): liver temperature was maintained during ischemia at 10°C, ischemic preconditioning group (IPC-IR) (n=14): 10 minutes of ischemia followed by 10 minutes of reperfusion prior to hepatic ischemia reperfusion and MitoQ treated group (n=11): MitoQ was injected intraperitoneally once before ischemia and another dose at start of reperfusion at a dose of 3mg/kg. ALT, AST and ALP were measured in serum while malondialdehyde (MDA), glutathione peroxidase (GPX), hypoxia inducible 1 alpha (HIF1α), tumor necrosis factor alpha (TNFα), cytochrome c (Cyt c), adenosine triphosphate (ATP) and dynamine related protein (DRP1) were measured in hepatic tissue in addition to the histological examination. Results: TH, IPC and MitoQ significantly reduced AST, MDA, TNFα, Cyt c and DRP1 expression. TH preserved hepatic integrity, normalized both AST and ALT, increased hepatic GPX and reduced MDA while IPC did not increase GPX and has less significantly reduced MDA compared to hypothermia. ATP was significantly higher with hypothermia compared to IPC and MitoQ. Hypothermia decreased significantly the level of HIF1α while preconditioning increased its level. Conclusion: Hypothermia and MitoQ treatment was more effective in ameliorating IR injury compared to IPC despite reduced metabolic reprogramming signal HIF1α which did not interfere with its protective effect. HIF1α high level with preconditioning did not confer added protection. Hypothermia induced its effect through improvement of REDOX state and mitochondrial bioenergetics. Key words: Ischemia reperfusion injury, Hepatic hypothermia, Hepatic ischemic preconditioning, Hypoxia inducible factor1 α (HIF1α), ATP. |