CISPLATIN NEPHROTOXICITY - INHIBITION OF GAMMA-GLUTAMYL-TRANSPEPTIDASE BLOCKS THE NEPHROTOXICITY OF CISPLATIN WITHOUT REDUCING PLATINUM CONCENTRATIONS IN THE KIDNEY

OBJECTIVE: Inhibition of gamma-glutamyl transpeptidase activity by aci vicin or a large bolus of intravenous glutathione blocks the nephrotox icity of cisplatin. The purpose of this study was to determine whether these compounds inhibit nephrotoxicity by reducing the amount of plat inum retained by the kidney. STUDY DESIGN: The platinum concentration in urine and kidney of cisplatin-treated rats was determined by graphi te furnace atomic absorption spectroscopy, Tissues from three experime ntal groups of rats were analyzed, The first group was treated with a nephrotoxic dose of cisplatin. The second group was treated with acivi cin before cisplatin. The third group received a bolus of glutathione before cisplatin. Urine collected for 3 hours after the injection of c isplatin and kidney tissue from animals 5 days after treatment were an alyzed for platinum content. RESULTS: Urine from animals pretreated wi th acivicin had the same concentration of platinum as that of control animals treated with cisplatin alone. Analysis of kidney tissue, blood urea nitrogen and serum creatinine 5 days after treatment; showed tha t pretreatment with acivicin or glutathione blocked the nephrotoxicity of cisplatin, However, these agents did not alter the concentration o f platinum in the kidney, CONCLUSIONS: The data in this study reveal t hat pretreatment with acivicin or glutathione does not block the uptak e of platinum into the kidney nor do these agents reduce the concentra tion of platinum retained by the kidney, The mechanism by which these agents may inhibit the nephrotoxicity of cisplatin is discussed.