Résumé
Ischemia-reperfusion injury is related with oxygen free radicals; a reason which has been suggested for this is the conversion of xanthine dehydrogenase (XDH) into xanthine oxidase (XO). In the present study, metabolic control of the enzymic conversion by modulating the cellular redox potential was attempted. An amino acid, aspartate, was tested as a possible candidate on the assumption that as a participant in the malate/aspartate shuttle, it might modify the cellular NADH/NAD+ balance. Its effect was studied by measuring the level of lipid peroxidation as a thiobarbituric acid-reactive substance (TEARS) and the conversion ratio of XDH to XO in the perfused-rat livers. The experimental animals, male Sprague Dawley rats were divided into three groups: control, ischemia and ischemia/reoxygenation. To each group, aspartate was infused at 2 mM level. ischemia alone did not affect the level of TEARS or the conversion ratio of the enzyme, regardless of aspartate infusion. In contrast, reoxygenation of previously ischemia liver significantly elevated the level of TEARS and decreased the ratio of XDH to XO; both this level and this ratio were ameliorated by aspartate. The protective role of aspartate against oxidative stress induced by ischemia/reoxygenation can be explained by the fact that aspartate may correct the increased NADH/NAD ratio by facilitating NAD regeneration from NADH through the coupled aspartate aminotransferase/malate dehydrogenase reaction and the malate-aspartate shuttle. Aspartate application may thus contribute to the development of a preventive strategy against ischemia/reperfusion-induced oxidative damages.