Experimental epothilone B neurotoxicity: results of in vitro and in vivo studies
| Autor: | Annalisa Canta, Ilaria Cervellini, Giuseppe Lauria, Norberto Oggioni, Raffaella Lombardi, Giacomo Cossa, Alessia Chiorazzi, Ilaria Roglio, Guido Cavaletti, Roberta Rigolio, Donatella Crippa, Roberto Bianchi, Roberto Cosimo Melcangi, Gabriella Nicolini |
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| Přispěvatelé: | Chiorazzi, A, Nicolini, G, Canta, A, Oggioni, N, Rigolio, R, Cossa, G, Lombardi, R, Roglio, I, Cervellini, I, Lauria, G, Melcangi, R, Bianchi, R, Crippa, D, Cavaletti, G |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Pain Threshold
Peripheral neuropathy Neurite Neurotoxins Neural Conduction In Vitro Techniques Pharmacology Epothilone lcsh:RC321-571 Rats Sprague-Dawley In vitro Tubulin In vivo Ganglia Spinal Neurites medicine Animals RNA Messenger Rats Wistar lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Myelin Sheath Skin Neurons Dose-Response Relationship Drug Toxicity biology Animal Chemistry Body Weight Neurotoxicity Neuron medicine.disease Sciatic Nerve Rats Inbred F344 Rats Neurology Epothilones Epothilone B biology.protein Rat Female Sciatic nerve Neurotoxin medicine.drug |
| Zdroj: | Neurobiology of Disease, Vol 35, Iss 2, Pp 270-277 (2009) |
| ISSN: | 1095-953X 0969-9961 |
| 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. |
| Databáze: | OpenAIRE |
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