Amifostine protects against chemotherapy-induced neurotoxicity: an in vitro investigation.
BACKGROUND
Peripheral neurotoxicity is a dose-limiting side-effect of a number of effective chemotherapeutic agents. Neuroprotective agents may help to reduce neurotoxicity, thus allowing the intensification of cytostatic therapy in patients.


METHODS
In this in vitro study, using the rat pheochromocytoma cell line PC-12 neurite-outgrowth assay, the potential of amifostine to protect against cisplatin-, paclitaxel- and vincristine-induced neurotoxicity was investigated Amifostine is described as selectively protecting normal tissue and not tumour tissue. The effect of amifostine on tumour cell kill was investigated using the XTT and colony forming assay.


RESULTS
Paclitaxel and vincristine both caused a significant reduction in the percentage of cells expressing neurites. Co-incubation with amifostine significantly increased this percentage of neurites in paclitaxel-induced neurotoxicity, but not in vincristine-induced neurotoxicity. Post-incubation of amifostine also proved to partly reverse already existing cisplatin-induced neurotoxicity, but not paclitaxel-, or vincristine-induced neurotoxicity. Amifostine did not protect tumour cells against cisplatin- and paclitaxel-induced tumour cytotoxicity, using the XTT assay. However, a stimulation of clonogenic capacity was observed when amifostine was coincubated with cisplatin.


CONCLUSIONS
Amifostine protects against paclitaxel-induced neurotoxicity, but not against vincristine-induced neurotoxicity in this in vitro model. Furthermore, amifostine has potential to reverse already existing cisplatin-induced neurotoxicity. The role of amifostine in the proliferative potential of tumour cells in vitro needs further investigation.
Department of Neurology, VU University Medical Center Amsterdam, The Netherlands.
Carla C P
CC
Verstappen
Tjeerd J
TJ
Postma
Albert A
AA
Geldof
Jan J
JJ
Heimans
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity; D006801:Humans; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D016716:PC12 Cells; D017239:Paclitaxel / Q000633:toxicity; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000188:drug therapy* / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology; D051381:Rats; D014750:Vincristine / Q000633:toxicity
D000970:Antineoplastic Agents; D014750:Vincristine; D004999:Amifostine; D017239:Paclitaxel; D002945:Cisplatin