BETAMIPRON REDUCES CISPLATIN NEPHROTOXICITY IN RODENTS WITHOUT MODIFYING ITS ANTILEUKEMIC ACTIVITY IN MICE

Protective effects of betamipron (BP, N-benzoyl-beta-alanine), one of a series of N-acyl amino acids, on cisplatin-induced nephrotoxicity we re examined. Since the damage observed in the kidney is localized to t he proximal tubule cells, we investigated the influence of BP on urina ry enzymes and excreta. Male Wistar rats and ddY mice were injected i. p. with 6 mg/kg and 16 mg/kg, respectively, of cisplatin combined with an i.p. 250 mg/kg BP dose. The toxicity of cisplatin as indicated by body weight gain, blood urea nitrogen, and serum creatinine levels was significantly (p < 0.05) suppressed by administration of BP after cis platin treatment. The increase in urinary N-acetyl-beta-D-glucosaminid ase activity, increase and subsequent decrease in gamma-glutamyl trans ferase activities, and increase in beta(2)-microglobulin level observe d after treatment with cisplatin were suppressed by administration of BP after cisplatin treatment. The combination of cisplatin and BP had no apparent effect on the efficacy of cisplatin against P388 leukemic cells in mice.