Our aim was 2-fold: to investigate the role of alpha-tocopherol supplementation on the antitumor activity of DDP and to evaluate the effect of alpha-tocopherol on the survival and neurotoxicity of DDP-treated mice. Experiments performed on the M14 human melanoma line demonstrated that alpha-tocopherol supplementation did not influence the efficacy of DDP; the inhibition of cell survival and of the in vivo tumor growth after treatment with alpha-tocopherol and DDP combination was similar to that observed after DDP alone. Conversely, alpha-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 alpha-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 alpha-tocopherol the levels of these markers were comparable to those observed in untreated mice. Histologic analysis performed on peripheral nerve revealed that alpha-tocopherol also protected mice from severe neurologic damage induced by DDP treatment. In conclusion, our results demonstrate that alpha-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.

Alpha-tocopherol protects against cisplatin-induced toxicity without interfering with anti tumor efficacy / Leonetti, C; Biroccio, A.; Gabellini, Chiara; Scarsella, M.; Maresca, V.; Flori, E.; Bove, L.; Pace, A.; Stoppacciaro, Antonella; Zupi, G.; Cognetti, F.; Picardo, M.. - In: INTERNATIONAL JOURNAL OF CANCER. - ISSN 0020-7136. - STAMPA. - 104:(2003), pp. 243-250. [10.1002/ijc.10933]

Alpha-tocopherol protects against cisplatin-induced toxicity without interfering with anti tumor efficacy.

GABELLINI, CHIARA;STOPPACCIARO, ANTONELLA;COGNETTI F.;
2003

Abstract

Our aim was 2-fold: to investigate the role of alpha-tocopherol supplementation on the antitumor activity of DDP and to evaluate the effect of alpha-tocopherol on the survival and neurotoxicity of DDP-treated mice. Experiments performed on the M14 human melanoma line demonstrated that alpha-tocopherol supplementation did not influence the efficacy of DDP; the inhibition of cell survival and of the in vivo tumor growth after treatment with alpha-tocopherol and DDP combination was similar to that observed after DDP alone. Conversely, alpha-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 alpha-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 alpha-tocopherol the levels of these markers were comparable to those observed in untreated mice. Histologic analysis performed on peripheral nerve revealed that alpha-tocopherol also protected mice from severe neurologic damage induced by DDP treatment. In conclusion, our results demonstrate that alpha-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.
01 Pubblicazione su rivista::01a Articolo in rivista
Alpha-tocopherol protects against cisplatin-induced toxicity without interfering with anti tumor efficacy / Leonetti, C; Biroccio, A.; Gabellini, Chiara; Scarsella, M.; Maresca, V.; Flori, E.; Bove, L.; Pace, A.; Stoppacciaro, Antonella; Zupi, G.; Cognetti, F.; Picardo, M.. - In: INTERNATIONAL JOURNAL OF CANCER. - ISSN 0020-7136. - STAMPA. - 104:(2003), pp. 243-250. [10.1002/ijc.10933]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/365851
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