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Topical Hypothermia is More Efficient Than Ischemic Preconditioning in Ameliorating Hepatic Ischemia Reperfusion Injury in Rat Liver Through Hypoxia Inducible Factor Independent Mechanisms.

Hepatic ischemia reperfusion (IR) injury is common with many medical strategies as liver transplantation and trauma. Aim: is comparing the efficacy and evaluating the possible mechanisms of ischemic preconditioning (IPC) and topical hypothermia (TH) in the hepatic IR injury. Method: 56 adult male albino rats were allocated into four 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. 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 and IPC 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. Hypothermia decreased significantly the level of HIF1α while preconditioning increased its level. Conclusion: Hypothermia was more protective against IR injury compared to IPC despite reduced metabolic reprogramming signal HIF1α. Hypothermia effect was through improvement of REDOX state and mitochondrial bioenergetics.