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.