Prevention of cisplatin-induced nephrotoxicity by methimazole

Nephrotoxicity is a dose-limiting factor in the use of cisplatin against so lid tumours. Methimazole, an antithyroid drug containing a free SH group, h as a nephroprotective potential against chemically-induced nephrotoxicity. We tried to explore the nephrotoxic effect of the experimentally therapeuti c dose of cisplatin (7 mg kg(-1), i.p.), particularly on the nuclear level of kidney cells in male albino rats, as well as the possible protective eff ect of methimazole. Furthermore, the drug interaction regarding the oncolyt ic effect of cisplatin was examined in Ehrlich ascites carcinoma (EAC)-bear ing mice. A single dose of cisplatin caused kidney damage, 6 days after inj ection, manifested by 219% increase in serum creatinine, 384% increase in b lood urea nitrogen and 170% increase in kidney content of lipid peroxides. Kidney DNA showed clear fragmentations detected by gel electrophoresis. How ever, kidney reduced glutathione was unchanged at that time period. Histolo gical examination of kidney confirmed the toxic effect of cisplatin. Methim azole (40 mg kg(-1), i.p., 30 min before cisplatin injection) significantly protected the kidney from the nephrotoxic effect of cisplatin as judged fr om the biochemical parameters investigated as well as the histopathological examination. On the other hand, the survival data in EAC-bearing mice trea ted with both drugs indicated the persistence of an effective cytotoxic act ion. This study points to a promising use of this combination and necessita tes further experimental and clinical studies. (C) 2000 Academic Press.