Effects of reduced glutathion and vitamin c on cisplatin-induced hepatotoxicity in rats

Abstract

Cisplatin (CDDP) is a widely used anticancer drug, however it can produce undesirable side effects such as hepatotoxicity when used at high doses . The aim of the present work to evaluate the protective effect of reduced glutathione (GSH) and vitamin C on CDDP-induced hepatotoxicity . Eighty male Sprague-Dawley rats were divided into eight groups, 10 rats each. Group I , control group. Group II received Cisplatin (7.5 mg /kg, i.p) for 5 consecutive days. Group III received GSH (600 mg/kg /day, i.p). Group IV received vitamin C (250 mg/kg/day, orally) . Group V received GSH for 15 days then CDDP for 5 days. Group VI administered vitamin C for 15 days then CDDP for 5 days. Group VII administered both GSH and CDDP for 5 days . The last Group (VIII) administered both vitamin C and CDDP for 5 days. Serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST] activities (markers of hepatotoxicity), antioxidants (superoxide dismutase [SOD], glutathione peroxidase [GSHPx], catalase [CAT], glutathione reductase [GSHR] activities and gene expression, glutathione [GSH] content) and lipid peroxidation products (malondialdehyde, MDA) in rat liver tissue were measured. CDDP hepatotoxicity was manifested by an increase in serum ALT and AST, elevation of MDA as well as a decrease in GSH and the activities and gene expression of antioxidant enzymes (SOD, GSHPx, CAT, GSHR) in liver tissues. Serum ALT, AST and hepatic MDA decreased in the combination groups in comparison with the CDDP group. The activities and gene expression of SOD, GSHPx, CAT and GSHR and the GSH concentration increased in the combination groups as compared to the CDDP group. Reduced glutathione and vitamin C either taken before or concomitant with cisplatin attenuated the CDDP hepatotoxicity. Key words : GSH , Vitamin C, CDP, Hepatotoxicity.