| Literature DB >> 19464369 |
Alessia Chiorazzi1, 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.
Abstract
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 muM) 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 x 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.Entities:
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Year: 2009 PMID： 19464369 DOI： 10.1016/j.nbd.2009.05.006
Source DB: PubMed Journal: Neurobiol Dis ISSN： 0969-9961 Impact factor: 5.996