Alleviation of Ischemia-Reperfusion Injury in Liver Steatosis by Augmenter of Liver Regeneration (ALR) Is Attributed to Antioxidation and Preservation of Mitochondria.

Background: Fatty liver is 1 of the major impediments to liver surgery and liver transplantation because steatotic hepatocytes are more susceptible to ischemia-reperfusion injury (IRI). In this study, the effects of augmenter of liver regeneration (ALR) on hepatic IRI in steatotic mice were investigated. Methods: In vivo, liver steatosis of mice was induced by feeding a methionine-choline deficient diet for 2 weeks. Three days prior to hepatic partial warm IRI, mice were transfected with the ALR-containing adenovirus. In an in vitro study, the protective effect of ALR on steatotic HepG2 cells was analyzed after hypoxia/reoxygenation (HR) treatment. Results: The transfection of the ALR gene into steatotic mice attenuated liver injury, inhibiting hepatic oxidative stress, increasing antioxidation capacities, promoting liver regeneration, and consequently suppressing cell apoptosis/death. Furthermore, resistance to HR injury was notably increased in ALR transfected cells compared to the vector transfected cells. The HR induced rise in the mitochondrial ROS was reduced, and cellular antioxidant activities were enhanced. The ALR transfection prevented cells from apoptosis can be attributed to the preservation of the mitochondrial membrane potential, enhancement of oxygen consumption rate (OCR) and production of ATP. Conclusions: ALR protects steatotic hepatocytes from IRI by attenuating oxidative stress and mitochondrial dysfunction, as well as improving antioxidant effect. ALR may be used as a potential therapeutic agent when performing surgery and transplantation of steatotic liver. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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