Ischemia-reperfusion injury is related with oxygenfree radicals; a reason which has been suggestedfor this is the conversion of xanthine dehydrogena-se(XDH) into xanthine oxidase (XO). In the presentstudy, metabolic control of the enzymic conversionby modulating the cellular redox potential wasattempted. An amino acid, aspartate, was tested asa possible candidate on the assumption that as aparticipant in the malate/aspartate shuttle, it mightmodify the cellular NADH/NAD+ balance. Its effectwas studied by measuring the level of lipid peroxi-dationas a thiobarbituric acid-reactive substance(TBARS) and the conversion ratio of XDH to XO inthe perfused-rat livers. The experimental animals,male Sprague Dawley rats were divided into threegroups: control, ischemia and ischemia/reoxygena-tion.To each group, aspartate was infused at 2 mM level. Ischemia alone did not affect the level ofTBARS or the conversion ratio of the enzyme, regardless of aspartate infusion. In contrast,reoxygenation of previously ischemia liver signifi-cantlyelevated the level of TBARS and decreasedthe ratio of XDH to XO; both this level and this ratiowere ameliorated by aspartate. The protective roleof aspartate against oxidative stress induced byischemia/ reoxygenation can be explained by thefact that aspartate may correct the increased NADH/NAD ratio by facilitating NAD regeneration fromNADH through the coupled aspartate aminotrans-ferase/malate dehydrogenase reaction and themalate-aspartate shuttle. Aspartate application maythus contribute to the development of a preventivestrategy against ischemia/reperfusion-inducedoxidative damages.