α‐tocopherol protects against cisplatin‐induced toxicity without interfering with antitumor efficacy

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Abstract
Our aim was 2‐fold: to investigate the role of α‐tocopherol supplementation on the antitumor activity of DDP and to evaluate the effect of α‐tocopherol on the survival and neurotoxicity of DDP‐treated mice. Experiments performed on the M14 human melanoma line demonstrated that α‐tocopherol supplementation did not influence the efficacy of DDP; the inhibition of cell survival and of the in vivo tumor growth after treatment with α‐tocopherol and DDP combination was similar to that observed after DDP alone. Conversely, α‐tocopherol was also able to increase survival of mice treated with a high dose of DDP. While DDP alone produced death in about 70% of mice, the combination reduced deaths to about 30%. Analysis of oxidative stress markers and peroxidative damage in organs indicated that the protective effect of α‐tocopherol was mainly related to its antioxidant activity. A significant increase in the concentration of TBARS and decreased PUFAs and catalase activity were observed after DDP treatment, while with α‐tocopherol the levels of these markers were comparable to those observed in untreated mice. Histologic analysis performed on peripheral nerve revealed that α‐tocopherol also protected mice from severe neurologic damage induced by DDP treatment. In conclusion, our results demonstrate that α‐tocopherol protects against the systemic toxicity and neurotoxicity induced by DDP without interfering with its antitumor activity and suggest that this combination is a promising strategy to improve the therapeutic index of DDP‐based chemotherapy.