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Paclitaxel induces nucleolar enlargement in dorsal root ganglion neurons in vivo reducing oxaliplatin toxicity
Jamieson, SMF and Liu, JJ and Hsu, T and Baguley, BC and McKeage, MJ, Paclitaxel induces nucleolar enlargement in dorsal root ganglion neurons in vivo reducing oxaliplatin toxicity, British Journal of Cancer, 88 pp. 1942-1947. ISSN 0007-0920 (2003) [Refereed Article]
Licenced under Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported (CC BY-NC-SA 3.0) http://creativecommons.org/licenses/by-nc-sa/3.0/
Official URL: http://www.nature.com/bjc/journal/v88/n12/full/660...
Paclitaxel and oxaliplatin are promising drugs for combination trials but both induce peripheral neurotoxicity. To investigate this toxicity, 10-week-old female Wistar rats were given single intraperitoneal doses of paclitaxel and oxaliplatin, alone or in combination. Neurotoxicity was assessed by L5 dorsal root ganglion morphometry and H-reflex-related sensory nerve conduction velocity. Platinum concentrations in dorsal root ganglia and plasma were measured by inductively coupled plasma mass spectrometry. Dorsal root ganglion nucleolus size was significantly increased following single doses of paclitaxel of 10 and 20 mg kg-1 at 24 h and 6 days (Po0.02). In contrast, dorsal root ganglion nucleolus size was significantly decreased following single doses of oxaliplatin ranging from 3 to 30mgkg-1 at time points ranging from 2 h to 14 days. Sensory nerve conduction velocity was altered after a single dose of oxaliplatin but not after paclitaxel. In combination with oxaliplatin, paclitaxel did not alter the plasma pharmacokinetics or dorsal root ganglion accumulation of oxaliplatin-derived platinum. However, prior paclitaxel inhibited oxaliplatin-induced reductions of dorsal root ganglion nucleolar diameter (Po0.02). Sensory nerve conduction velocity was reduced after oxaliplatin alone (Po0.05) but unchanged when paclitaxel was given before oxaliplatin. In conclusion, paclitaxel induces nucleolar enlargement in dorsal root ganglion neurons after pharmacologically relevant doses in vivo and reduces oxaliplatin nucleolar damage and neurotoxicity.
|Item Type:||Refereed Article|
|Keywords:||paclitaxel;neurotoxicity; rat dorsal root gangliion|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Pharmacology and pharmaceutical sciences|
|Research Field:||Clinical pharmacology and therapeutics|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Liu, JJ (Dr Johnson Liu)|
|Downloads:||362 View Download Statistics|
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