Experimental epothilone B neurotoxicity: Results of in vitro and in vivo studies

Autor: Alessia Chiorazzi, Gabriella Nicolini, Annalisa Canta, Norberto Oggioni, Roberta Rigolio, Giacomo Cossa, Raffaella Lombardi, Ilaria Roglio, Ilaria Cervellini, Giuseppe Lauria, Roberto Cosimo Melcangi, Roberto Bianchi, Donatella Crippa, Guido Cavaletti
Jazyk: angličtina
Rok vydání: 2009
Předmět:
Zdroj: Neurobiology of Disease, Vol 35, Iss 2, Pp 270-277 (2009)
Druh dokumentu: article
ISSN: 1095-953X
DOI: 10.1016/j.nbd.2009.05.006
Popis: 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.
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