The reduced tolerance of rat fatty liver to ischemia reperfusion is associated with mitochondrial oxidative injury.

BACKGROUND: Oxidative stress contributes to the pathogenesis of hepatic ischemia-reperfusion injury. This study aimed to determine whether fatty degeneration affects the oxidative damage during warm ischemia reperfusion and whether mitochondria, the major intracellular site of energy synthesis, represent a preferential target of this injury.
MATERIALS AND METHODS: Fed rats with control or fatty liver induced by choline deficiency underwent 60' lobar ischemia and reperfusion. Oxidative damage was assessed by measuring in whole liver tissue and in isolated mitochondria the thiobarbituric acid-reactive substances (TBARs), protein carbonyls (PC), and total and oxidized glutathione (GSH and GSSG) concentrations. The mitochondrial F0-F1-ATPase content and the oxidative phosphorylation activity were also determined. Rat survival and ALT release were assessed as parameters of liver injury.
RESULTS: In the whole liver tissue, with the exception of TBARs, no differences were observed for GSH, GSSG, and PC between the two groups throughout all of the experiment. In contrast, in isolated mitochondria, fatty infiltration was associated with a mild oxidative imbalance already under basal conditions. The preischemic differences in the mitochondrial TBARs, PC, and GSSG levels were significantly amplified by reperfusion in the presence of steatosis. The enhanced oxidative damage was associated to a reduced F0-F1-ATPase content and oxidative phosphorylation activity in fatty liver mitochondria. Finally, serum ALT levels were significantly greater and survival significantly lower in rats with steatotic liver.
CONCLUSIONS: Fatty infiltration exacerbates mitochondrial oxidative injury during warm ischemia reperfusion. The increased oxidative stress can alter mitochondrial functions, including key processes for ATP synthesis, thus, contributing to the reduced tolerance to reperfusion injury.