Cis-dichlorodianunineplatinum(II) (cisplatin (CDDP) ) is one of' the most effective antitumor agents currently available for cancer therapy. I lowever, its clinical use has been limited by its severe side effects, especially nephrotoxicity. To evaluate the effect of radical scavengers on CDDP nephrotoxicity in rats, CDDP and Vitamin C were given intrapcritoneally. Remarkable protective effects o1' Vitamin C against nephrotoxicity of' CDDP were observed when Vitamin C and GSII were administered to rats before or with CDDP injection. Vitamin C which has radical scavenging effect directly reduced nephrotoxicity of CDDP in vivo. Thus, it seems that free radical is the cause of CDDP nephrotoxicity. Also, combination treatment did not reduce anticancer activity of CDDP. The present results indicate that Vitamin C, and/or GSH when there were given before or with CDllI', may provide protection against CDDP nephrotoxicity without reducing anticancer activity. The aim of the present study was to investigate whether or not the renal antioxidant system plays also an important role in renal damage induced CDDP (2 mg/kg intrapcritoneally at a single does in rats). In order to elucidate it, serum creatininc and urea levels, renal glutathione and thiobarbituric acid-reactive substances (TBARS) content, as well as renal catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSHpx) activities were measured in the kidney homogenates and additionally of gene expression of GSHpx and glutathione reductase (GRD) were determined.