ROLE OF GLUTATHIONE-S-TRANSFERASE ISOENZYMES IN CISPLATIN-INDUCED NEPHROTOXICITY IN THE RAT

cis-Diamminedichloroplatinum(II) (cisplatin) is an effective antitumor agent but causes dose-dependent nephrotoxicity. We examined the chang es of glutathione S-transferase (GST) isoenzymes in the rat kidney aft er cisplatin administration. Renal GST-alpha activity was decreased to 33.4% of the control level and GST-mu activity was increased 1.9-fold after cisplatin administration. These results were confirmed by affin ity chromatography of rat renal GST isoenzymes. Our results showed tha t changes of GST isoenzymes were associated with cisplatin-induced nep hrotoxicity. We examined whether GST isoenzymes leaked into the urine by proximal tubular damage could provide a useful marker of cisplatin- induced nephrotoxicity. The total GST and GST-mu activities in urine c orrelated well with the changes of BUN, which closely parallels the co urse of nephrotoxicity after cisplatin administration. Our results ind icated that renal GST-mu activity was decreased by cisplatin, and alth ough GST-mu activity increased as a compensation mechanism, nephrotoxi city still appeared because of differences in substrate specificity be tween these two isoenzymes.