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Oxaliplatin-induced loss of phosphorylated heavy neurofilament subunit neuronal immunoreactivity in rat DRG tissue

Citation

Jamieson, SMF and Subramaniam, J and Liu, JJ and Jong, NN and Connor, B and McKeage, MJ, Oxaliplatin-induced loss of phosphorylated heavy neurofilament subunit neuronal immunoreactivity in rat DRG tissue, Molecular Pain, 5, (66) pp. 1-9. ISSN 1744-8069 (2009) [Refereed Article]


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Copyright Statement

Copyright 2009 The Authors-This is an Open Access article distributed under the terms of the Creative Commons Attribution License (CC BY 2.0 AU).(http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

DOI: doi:10.1186/1744-8069-5-66

Abstract

Abstract Background: Oxaliplatin and related chemotherapeutic drugs cause painful chronic peripheral neuropathies in cancer patients. We investigated changes in neuronal size profiles and neurofilament immunoreactivity in L5 dorsal root ganglion (DRG) tissue of adult female Wistar rats after multiple-dose treatment with oxaliplatin, cisplatin, carboplatin or paclitaxel. Results: After treatment with oxaliplatin, phosphorylated neurofilament heavy subunit (pNF-H) immunoreactivity was reduced in neuronal cell bodies, but unchanged in nerve fibres, of the L5 DRG. Morphometric analysis confirmed significant changes in the number (-75%; P < 0.0002) and size (-45%; P < 0.0001) of pNF-H-immunoreactive neurons after oxaliplatin treatment. pNF-Himmunoreactive neurons had overlapping size profiles and co-localisation with neurons displaying cell body immunoreactivity for parvalbumin, non-phospho-specific neurofilament medium subunit (NF-M) and non-phospho-specific neurofilament heavy subunit (NF-H), in control DRG. However, there were no significant changes in the numbers of neurons with immunoreactivity for parvalbumin (4.6%, P = 0.82), NF-M (-1%, P = 0.96) or NF-H (0%; P = 0.93) after oxaliplatin treatment, although the sizes of parvalbumin (-29%, P = 0.047), NF-M (-11%, P = 0.038) and NF-H (-28%; P = 0.0033) immunoreactive neurons were reduced. In an independent comparison of different chemotherapeutic agents, the number of pNF-H-immunoreactive neurons was significantly altered by oxaliplatin (-77.2%; P < 0.0001) and cisplatin (-35.2%; P = 0.03) but not by carboplatin or paclitaxel, and their mean cell body area was significantly changed by oxaliplatin (- 31.1%; P = 0.008) but not by cisplatin, carboplatin or paclitaxel. Conclusion: This study has demonstrated a specific pattern of loss of pNF-H immunoreactivity in rat DRG tissue that corresponds with the relative neurotoxicity of oxaliplatin, cisplatin and carboplatin. Loss of pNF-H may be mechanistically linked to oxaliplatin-induced neuronal atrophy, and serves as a readily measureable endpoint of its neurotoxicity in the rat model.

Item Details

Item Type:Refereed Article
Keywords:oxaliplatin, neurotoxicity, neurofilament
Research Division:Medical and Health Sciences
Research Group:Pharmacology and Pharmaceutical Sciences
Research Field:Clinical Pharmacology and Therapeutics
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Cancer and Related Disorders
Author:Liu, JJ (Dr Johnson Liu)
ID Code:89122
Year Published:2009
Web of Science® Times Cited:16
Deposited By:Pharmacy
Deposited On:2014-02-25
Last Modified:2014-06-18
Downloads:619 View Download Statistics

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