In vitro protection from cisplatin-induced neurotoxicity by amifostine and its metabolite WR1065.
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 microg/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.
Verstappen
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CC
Department of Neurology, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Geldof
A A
AA
Postma
T J
TJ
Heimans
J J
JJ
D004999:Amifostine / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D008624:Mercaptoethylamines / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D016716:PC12 Cells; D051381:Rats
D000970:Antineoplastic Agents; D008624:Mercaptoethylamines; D018696:Neuroprotective Agents; D009498:Neurotoxins; C020174:N-(2-mercaptoethyl)-1,3-diaminopropane; D004999:Amifostine; D002945:Cisplatin