Experimental epothilone B neurotoxicity: Results of in vitro
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- 作者：Alessia Chiorazzi ; Gabriella Nicolini ; Annalisa Canta ; Norberto Oggioni ; Roberta Rigolio ; Giacomo Cossa ; Raffaella Lombardi ; Ilaria Roglio ; Ilaria Cervellini ; Giuseppe Lauria ; Roberto Cosimo Melcangi
- 关键词：Epothilone B ; In vivo ; In vitro ; Toxicity ; Peripheral neuropathy ; Tubulin
- 刊名：Neurobiology of Disease
- 出版年：2009
- 出版时间：August 2009
- 年：2009
- 卷：35
- 期：2
- 页码：270-277
- 全文大小：1067 K
文摘
Epothilones are a novel class of microtubule-targeting anticancer agents that are neurotoxic. In this study, we investigated the epothilone B toxic effect in vitro and we characterized in vivo the general and neurological side effects of epothilone B administration in Wistar and Fischer rats.
The in vitro experiments made it possible to explore a wide concentration range (0.1 nM–1 μM) and evidenced a dose-dependent effect of epothilone B exposure on neuron neurite elongation. This dose-dependent neurotoxic effect was confirmed in both in vivo studies performed on two different rat strains at the neurophysiological, behavioral and pathological levels in the dose range 0.25–1.5 mg/kg iv weekly × 4 weeks and tubulin hyper-polymerization was demonstrated in sciatic nerve specimens.
These are the first studies of the neurological effects of epothilone B and they can provide a basis for extending pre-clinical investigation to other members of the epothilone family.