Protective Effects of .ALPHA.-Tocopherol against Glucose Intolerance and Mitochondrial Damage in Reperfused Rat Liver.

Abstract

We examined the protective effects of α-tocopherol against glucose intolerance and mitochondrial damage in rat liver after partial in vivo ischemia and reperfusion, while glucose was intravascularly supplemented. Rats were given α-tocopherol or vehicle for three consecutive days before the experiment. Left and median lobes of the liver received 90-min ischemia and 60-min reperfusion. Besides plasma levels of glucose, insulin, and lipid peroxide, we also measured oxidative phosphorylation, cytochrome c oxidase (CCO) activity, and lipid peroxide levels in mitochondria in both ischemic and non-ischemic lobes of the liver in control and α-tocopherol groups before and at the end of ischemia and after reperfusion. Both plasma glucose and insulin levels after reperfusion were lower in the α-tocopherol-treated group than in the control group. Ischemia markedly suppressed both mitochondrial respiration supported by succinate and CCO activity in the ischemic lobes in both groups. Reperfusion recovered mitochondrial function and CCO activity better in the α-tocopherol-treated group than in the control group, whereas the lipid peroxide levels in both plasma and mitochondria were significantly lower in the α-tocopherol-treated group. In non-ischemic lobes, ischemia-reperfusion slightly accelerated both the oxidative phosphorylation rate (OPR) and CCO activity, whereas lipid peroxide levels were unaffected. The results suggest that glucose intolerance during the early phase of reperfusion was not due to lowered plasma insulin level, but might be related to liver damage, as assessed in terms of mitochondrial functions, in the ischemic lobes. α-Tocopherol could protect against mitochondrial damage and glucose intolerance. Oxidative phosphorylation in non-ischemic lobes likely compensated for the decreased mitochondrial activity in the ischemic lobes during ischemia and reperfusion.