EJMS

Abstract

Most anticancer agents cause toxicity in various organs by disturbing the oxidant/antioxidant balance. Cisplatin is considered one of the most effective antineoplastic drugs for tens of years. However, its use is associated with lots of adverse effects that may be fatal, such as nephrotoxicity and ototoxicity. Besides, hepatotoxicity may result from cisplatin administration, with higher doses. The present experiment was conducted to assess the potential protection offered by using Diphenyl Dimethyl Bicarboxylate (DDB) and Ginkgo biloba Extract (GBE) against cisplatin nephrotoxicity and hepatotoxicity. Male rats were divided into 6 groups; of 8 rats. The control was given saline IP, DDB and GBE were given for 3 days alone (groups 2,3), cisplatin (10 mg/kg, IP) was given once on the first day of treatment (group 4). One hour after cisplatin administration, DDB and GBE were given orally to animals at doses of 150 and 200 mg/kg/day respectively for 3 days (groups 5,6). Seventy two hours after cisplatin administration, animals were sacrificed, where blood withdrawal and liver isolation were carried out. Serum levels of ALT, AST, ALP, total protein and albumin were measured. The oxidative stress and antioxidant measures (GSH, MDA content and SOD level) were evaluated in rats’ livers. DDB and GBE treated groups were compared with the control and toxic cisplatin treated group. According to the result, cisplatin caused a significant increase (P<0.05) in all biochemical parameters (AST, ALT and ALP) but a significant decrease in serum levels of total protein and albumin) compared to the control group. However, DDB and GBE moderately decreased AST, ALT and ALP levels compared to cisplatin-treated rats, while serum total protein and albumin levels were slightly increased when compared to the cisplatin-treated rats. The oxidative stress parameter MDA was significantly increased in liver tissues cisplatin-treated rats, while GSH was significantly decreased (P<0.05). DDB and GBE improved the oxidative stress parameters. The antioxidant SOD activity was significantly decreased (P<0.05) with cisplatin alone. In cisplatin-treated rats which received DDB or GBE, the SOD activity was significantly increased (P<0.05) when compared with the toxic group. In conclusion, DDB and GBE offered a partial protective effect against cisplatin hepatotoxicity, and DDB hepatoprotective effects seem to be more pronounced than GBE.