Contribution of gamma glutamyl transpeptidase to oxidative damage of ischemic rat kidney

BACKGROUND: A variety of mechanisms have been considered in the pathogenesis of the cell damage occurring in the kidney that is undergoing transient ischemia. However, little information is available about the role of oxidative stress in building up the tissue injury in the hypoxic organ during short-term ischemia. METHODS: After a standard brief period (25 min) of unilateral kidney ischemia in rats, pretreated or not with acivicin (60 micromol/L/kg i.v.), tissue samples from both ischemic and not ischemic kidneys were obtained to measure malondialdehyde (MDA) and glutathione (GSH) content, gamma glutamyl transpeptidase (GGT) activity by spectrophotometry, localization and intensity of enzyme activity, and tissue damage by histochemistry. RESULTS: GGT activity was found to be increased in both cortical and medullar zones of the ischemic kidneys, where the GSH level was only slightly decreased and the MDA level, in contrast, was markedly increased; in parallel, the cytosolic volume of the proximal tubular (PT) cells showed a significant increment. The animal pretreatment with acivicin, a specific inhibitor of GGT, besides preventing the up-regulation of the enzyme during ischemia, afforded good protection against the observed changes of MDA and GSH tissue levels, as well as of tubular cell volume. CONCLUSIONS: Ex vivo data supporting a net pro-oxidant effect of up-regulated GGT during short-term ischemia of rat kidney have been obtained. The enzyme stimulation appears to contribute to the renal morphological damage exerted by a brief hypoxic condition at the level of PT cells. The actual impact on kidney function by GGT-dependent oxidative damage during transient ischemia and the potential protective action of GGT inhibitors require subsequent investigation.