Effect of vitamin C supplementation against cisplatin-induced toxicity and oxidative DNA damage in rats.

Antitumor agents are used as a common therapy against some kinds of cancer. However, as with many agents that have mammalian cell toxicity as a target, physiological adverse effects can occur such as nephrotoxicity and genotoxicity that can be induced in non-tumor cells by generating activated oxygen species, which attack the DNA frequently resulting in oxidative DNA damage. To diminish the undesirable side-effects of therapy and to reduce the levels of oxidative DNA damage, it is recommended for patients to ingest food supplements and vitamins combinations containing substantial amounts of antioxidants. In the present study, we investigated the effects of cisplatin and vitamin C on the renal toxicity and on the oxidative DNA damage. Rats were co-treated with the chemotherapeutic agent cisplatin (5 mg kg(-1) body weight) and dietary doses of vitamin C (50 and 100 mg kg(-1) body weight). Results demonstrated that depending on the treatment protocol, we observed alterations in parameters such as body weight, urinary volume and urinary creatinine, indicating some kidney toxicity. We also observed changes in the urinary levels of 8-OHdG, suggesting possible oxidative DNA damage.

Protective effects of vitamin c against cisplatin-induced nephrotoxicity and lipid peroxidation in adult rats: a dose-dependent study.

Cisplatin is one of the most active cytotoxic agents in the treatment of cancer, but its clinical use is associated with nephrotoxicity. In the present study we report the effects of different amounts of vitamin C (50, 100 or 200 mg kg(-1)body wt.) in rat kidneys treated with cisplatin (5 mg kg(-1)body wt.), using single doses of both compounds. Cisplatin administration induced lipid peroxidation which was accompanied by a decrease in renal glutathione level in animals killed 7 days after treatments. Furthermore, an increase in serum creatinine has been observed. Treatment of animals with vitamin C 10 min prior to the cisplatin inhibited cisplatin-mediated damage. Seven days after vitamin C plus cisplatin treatments, the depleted level of glutathione and changes in the creatinine clearance recovered to significant levels (P<0.05). Similarly, the enhanced serum creatinine levels which are indicative of renal injury showed a significant reduction (P<0.05) with the three doses of vitamin C tested. The protective effect of vitamin C was dose-dependent. The results suggest that vitamin C is an effective chemoprotective agent against nephrotoxicity induced by the antitumoral cisplatin in Wistar adult rats.