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

Chiorazzi, A., Nicolini, G., Canta, A., Oggioni, N., Rigolio, R., Cossa, G., et al. (2009). Experimental epothilone B neurotoxicity: Results of in vitro and in vivo studies. NEUROBIOLOGY OF DISEASE, 35(2), 270-277 [10.1016/j.nbd.2009.05.006].

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

CHIORAZZI, ALESSIA;NICOLINI, GABRIELLA;Canta, A;OGGIONI, NORBERTO;RIGOLIO, ROBERTA;CAVALETTI, GUIDO ANGELO
2009

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
Articolo in rivista - Articolo scientifico
Female; Rats, Wistar; Myelin Sheath; Rats; Dose-Response Relationship, Drug; Animals; Skin; Body Weight; Rats, Sprague-Dawley; Neurotoxins; Epothilones; Tubulin; Neural Conduction; RNA, Messenger; Ganglia, Spinal; Neurons; Rats, Inbred F344; Pain Threshold; Sciatic Nerve; Neurites
English
2009
35
2
270
277
none
Chiorazzi, A., Nicolini, G., Canta, A., Oggioni, N., Rigolio, R., Cossa, G., et al. (2009). Experimental epothilone B neurotoxicity: Results of in vitro and in vivo studies. NEUROBIOLOGY OF DISEASE, 35(2), 270-277 [10.1016/j.nbd.2009.05.006].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/21051
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