In vitro protection from cisplatin-induced neurotoxicity by amifostine and its metabolite WR1065

C. C.P. Verstappen, A. A. Geldof, T. J. Postma, J. J. Heimans

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Cisplatin-induced neuropathy is a major dose-limiting toxicity. Counteraction by amifostine and its metabolite WR1065 may reduce peripheral neurotoxicity in a number of patients. Using the nerve growth factor (NGF)-dependent neurite outgrowth from the PC12 pheochromocytoma cell line as an in vitro assay for neurotoxicity, the protective effects of amifostine and WR1065 against cisplatin action on neurite formation by PC12 cells were studied. Cisplatin in a concentration of 10 μg/ml significantly decreased the percentage of neurite forming cells from 84% to 40%. Amifostine in doses of 0.4 and 0.8 mM proved to protect significantly against the cisplatin-induced decrease in neurite formation, when co-incubated with cisplatin. Also the metabolite WR1065 protected significantly against cisplatin neurotoxicity in a dose of 0.12 mM. Our results show a significant protection by amifostine and its main metabolite WR1065 against cisplatin-induced neurotoxicity using an in vitro model.

Original languageEnglish
Pages (from-to)1-5
Number of pages5
JournalJournal of Neuro-Oncology
Volume44
Issue number1
DOIs
Publication statusPublished - 17 Nov 1999

Cite this

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title = "In vitro protection from cisplatin-induced neurotoxicity by amifostine and its metabolite WR1065",
abstract = "Cisplatin-induced neuropathy is a major dose-limiting toxicity. Counteraction by amifostine and its metabolite WR1065 may reduce peripheral neurotoxicity in a number of patients. Using the nerve growth factor (NGF)-dependent neurite outgrowth from the PC12 pheochromocytoma cell line as an in vitro assay for neurotoxicity, the protective effects of amifostine and WR1065 against cisplatin action on neurite formation by PC12 cells were studied. Cisplatin in a concentration of 10 μg/ml significantly decreased the percentage of neurite forming cells from 84{\%} to 40{\%}. Amifostine in doses of 0.4 and 0.8 mM proved to protect significantly against the cisplatin-induced decrease in neurite formation, when co-incubated with cisplatin. Also the metabolite WR1065 protected significantly against cisplatin neurotoxicity in a dose of 0.12 mM. Our results show a significant protection by amifostine and its main metabolite WR1065 against cisplatin-induced neurotoxicity using an in vitro model.",
keywords = "Amifostine, Cisplatin, Neurotoxicity, PC12 cells",
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In vitro protection from cisplatin-induced neurotoxicity by amifostine and its metabolite WR1065. / Verstappen, C. C.P.; Geldof, A. A.; Postma, T. J.; Heimans, J. J.

In: Journal of Neuro-Oncology, Vol. 44, No. 1, 17.11.1999, p. 1-5.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - In vitro protection from cisplatin-induced neurotoxicity by amifostine and its metabolite WR1065

AU - Verstappen, C. C.P.

AU - Geldof, A. A.

AU - Postma, T. J.

AU - Heimans, J. J.

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N2 - Cisplatin-induced neuropathy is a major dose-limiting toxicity. Counteraction by amifostine and its metabolite WR1065 may reduce peripheral neurotoxicity in a number of patients. Using the nerve growth factor (NGF)-dependent neurite outgrowth from the PC12 pheochromocytoma cell line as an in vitro assay for neurotoxicity, the protective effects of amifostine and WR1065 against cisplatin action on neurite formation by PC12 cells were studied. Cisplatin in a concentration of 10 μg/ml significantly decreased the percentage of neurite forming cells from 84% to 40%. Amifostine in doses of 0.4 and 0.8 mM proved to protect significantly against the cisplatin-induced decrease in neurite formation, when co-incubated with cisplatin. Also the metabolite WR1065 protected significantly against cisplatin neurotoxicity in a dose of 0.12 mM. Our results show a significant protection by amifostine and its main metabolite WR1065 against cisplatin-induced neurotoxicity using an in vitro model.

AB - Cisplatin-induced neuropathy is a major dose-limiting toxicity. Counteraction by amifostine and its metabolite WR1065 may reduce peripheral neurotoxicity in a number of patients. Using the nerve growth factor (NGF)-dependent neurite outgrowth from the PC12 pheochromocytoma cell line as an in vitro assay for neurotoxicity, the protective effects of amifostine and WR1065 against cisplatin action on neurite formation by PC12 cells were studied. Cisplatin in a concentration of 10 μg/ml significantly decreased the percentage of neurite forming cells from 84% to 40%. Amifostine in doses of 0.4 and 0.8 mM proved to protect significantly against the cisplatin-induced decrease in neurite formation, when co-incubated with cisplatin. Also the metabolite WR1065 protected significantly against cisplatin neurotoxicity in a dose of 0.12 mM. Our results show a significant protection by amifostine and its main metabolite WR1065 against cisplatin-induced neurotoxicity using an in vitro model.

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