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RAT in vivo models of taxanes’ peripheral neurotoxicity following chronic intravenous administration
Author(s) -
Canta A,
Lanzani F,
Galbiati S,
Frigeni B,
Giussani G,
Marmiroli P,
Tredici G,
Traebert M,
Müller L,
Cavaletti G
Publication year - 2004
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1111/j.1085-9489.2004.009209b.x
Subject(s) - neurotoxicity , paclitaxel , docetaxel , tolerability , medicine , in vivo , pharmacology , toxicity , peripheral , nerve conduction velocity , anesthesia , chemotherapy , adverse effect , biology , microbiology and biotechnology
The “taxanes” family includes some widely used antineoplastic agents, such as paclitaxel and docetaxel. Treatment with these microtubule‐stabilizing drugs is often associated with neurotoxicity, a potentially severe side effect limiting the clinical utility of these agents. To study the pathogenesis of taxanes’ neurotoxicity and to compare it to the effect of new agents, the availability of reliable in vivo models is warranted. In this study we developed chronic iv models for the assessment of “taxanes” peripheral neurotoxicity. Forty‐eight adult Wistar rats were divided into six groups of 8 animals each and treated as follows: paclitaxel or docetaxel at doses of 5, 10, 12.5 mg/kg 1q7d × 4 via a chronic jugular vein implant. The evaluation was based on the assessment of body weight and survival as a measure of general tolerability, and on the measurement of tail nerve conduction velocity, a neurophysiological method previously used in animal models of toxic peripheral neuropathies. The results were compared with those obtained in untreated or vehicle‐treated control rats. A clear dose‐dependent effect was evident both on general toxicity, and on neurophysiological changes measured at the end of the treatment (untreated controls = 41,9 m/sec, vehicle = 40,3 m/sec; paclitaxel 5 mg/kg = 32,5 m/sec, 10 mg/kg = 28,5 m/sec, 12.5 m/kg = 27,4 m/sec; docetaxel 5 mg/kg = 33,6 m/sec, 10 mg/kg = 27,8 m/sec, 12.5 mg/kg = 27,0 m/sec), demonstrating the usefulness of this new model system to investigate peripheral neurotoxicity mediated by taxanes, and potentially other drugs, under chronic treatment schedules.