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

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

Neurobiology of Disease (Aug 2009)

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

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

Affiliations

Alessia Chiorazzi: Department of Neuroscience and Biomedical Technologies, University of Milan Bicocca, Monza, Italy; Corresponding author. Fax: +39 02 6448 8250.
Gabriella Nicolini: Department of Neuroscience and Biomedical Technologies, University of Milan Bicocca, Monza, Italy
Annalisa Canta: Department of Neuroscience and Biomedical Technologies, University of Milan Bicocca, Monza, Italy
Norberto Oggioni: Department of Neuroscience and Biomedical Technologies, University of Milan Bicocca, Monza, Italy
Roberta Rigolio: Department of Neuroscience and Biomedical Technologies, University of Milan Bicocca, Monza, Italy
Giacomo Cossa: Department of Neuroscience and Biomedical Technologies, University of Milan Bicocca, Monza, Italy
Raffaella Lombardi: Neuromuscular Diseases Unit, IRCCS National Neurological Institute “Carlo Besta” Foundation, Milan, Italy
Ilaria Roglio: Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy
Ilaria Cervellini: “M. Negri” Institute for Pharmacologic Research, Milan, Italy
Giuseppe Lauria: Neuromuscular Diseases Unit, IRCCS National Neurological Institute “Carlo Besta” Foundation, Milan, Italy
Roberto Cosimo Melcangi: Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Milan, Italy
Roberto Bianchi: “M. Negri” Institute for Pharmacologic Research, Milan, Italy
Donatella Crippa: Bayer Health Care-Bayer Schering Pharma, Milan, Italy
Guido Cavaletti: Department of Neuroscience and Biomedical Technologies, University of Milan Bicocca, Monza, Italy

Journal volume & issue: Vol. 35, no. 2
pp. 270 – 277

Abstract

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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.

Published in Neurobiology of Disease

ISSN: 0969-9961 (Print); 1095-953X (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neurosciences. Biological psychiatry. Neuropsychiatry
Website: https://www.journals.elsevier.com/neurobiology-of-disease

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