Hepatoprotective effects of vitamin C, DPPD, and L-cysteine against cisplatin-induced oxidative stress in male rats

Abstract

Cisplatin (CP) is considered as a major antineoplastic drug against a broad spectrum of malignancies. CP acts on cancer cells by releasing free radicals which at the same time damage liver and kidney cells. The tissue specific toxicity of cisplatin to the kidneys is well documented. However, at higher doses less common toxic effects such as hepatotoxicity may arise. Strategies to protect tissues against CP toxicity are of clinical interest. In this study, we aimed to investigate the hepatotoxicity of CP which it may be mediated by oxidative stress and to establish whether some antioxidants, namely vitamin C, N,N-diphenyl-р-phenylenediamine (DPPD) and L-cysteine, may provide protection against CP hepatotoxicity. Forty adult male albino rats (120-150 g) were divided into 5 groups (8 rats each). CP was injected once a week (2 mg/kg) for four weeks. The antioxidants DPPD (125 mg/kg b.w.), vitamin C (100 mg/kg) and L-cysteine (100 mg/kg) were also injected once a week 24 hour prior to CP injection. The control group was injected with saline. All doses were injected intraperitoneally. Rats of different groups were killed by cervical dislocation, 24 hours after the last injection and blood was collected into a sterilized tube containing EDTA to separate plasma. The livers was taken for histological and biochemical examinations. CP-induced oxidative stress was indicated by increased level of LPO and superoxide anion in hepatic tissue and plasma. Also, CP induced decline of antioxidant enzymes such as SOD, CAT, GST and GGT and a decreased level of GSH, Vit. C and Vit. E in hepatic tissue and plasma. Treatment with Vit. C, DPPD and L-cysteine in combination with CP restored LPO and superoxide anion, the activities of SOD, GST, CAT and GGT and the content of GSH, Vit. C and Vit. E to about normal control levels. in conclusion treatment with Vit. C, DPPD or L-cysteine in combination with CP may be effective to protect from oxidative hepatic injury that induced by CP treatment.

Keywords

• Cisplatin
• Hepatotoxicity
• DPPD
• Vitamin C
• L-cysteine
• Oxidative stress
• Rats
• Chemotherapy