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

Background. A variety of mechanisms have been considered in the pathogenesi s of the cell damage occurring in the kidney that is undergoing transient i schemia. However, little information is available about the role of oxidati ve stress in building up the tissue injury in the hypoxic organ during shor t-term ischemia. Methods. After a standard brief period (25 min) of unilateral kidney ischem ia in rats, pretreated or not with acivicin (60 mu mol/L/kg i.v.), tissue s amples from both ischemic and not ischemic kidneys were obtained to measure malondialdehyde (MDA) and glutathione (GSN) content, gamma gluramyl transp eptidase (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 medull ar zones of the ischemic kidneys, where the GSH level was only slightly dec reased and the MDA level, in contrast, was markedly increased; in parallel, the cytosolic volume of the proximal tubular (PT) cells showed a significa nt increment. The animal pretreatment with acivicin, a specific inhibitor o f GGT, besides preventing the up-regulation of the enzyme during ischemia, afforded good protection against the observed changes of MDA and GSN tissue levels, as well as of tubular cell volume. Conclusions. Ex vivo data supporting a net pro-oxidant effect of up-regulat ed GGT during short-term ischemia of rat kidney have been obtained. The enz yme stimulation appears to contribute to the renal morphological damage exe rted by a brief hypoxic condition at the level of PT cells. The actual impa ct on kidney function by GCT-dependent oxidative damage during transient is chemia and the potential protective action of GGT inhibitors require subseq uent investigation.