Abstract | BACKGROUND: 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-H-immunoreactive 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.
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Authors | Stephen M F Jamieson, Joshuan Subramaniam, Johnson J Liu, Nancy N Jong, Virginia Ip, Bronwen Connor, Mark J McKeage |
Journal | Molecular pain
(Mol Pain)
Vol. 5
Pg. 66
(Nov 18 2009)
ISSN: 1744-8069 [Electronic] United States |
PMID | 19922644
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Neurofilament Proteins
- Organoplatinum Compounds
- Oxaliplatin
- Carboplatin
- Paclitaxel
- Cisplatin
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Topics |
- Animals
- Antineoplastic Agents
(adverse effects, pharmacology)
- Carboplatin
(adverse effects, pharmacology)
- Cisplatin
(adverse effects, pharmacology)
- Female
- Ganglia, Spinal
(cytology, drug effects)
- Immunohistochemistry
- Neurofilament Proteins
(metabolism)
- Neurons
(cytology, drug effects)
- Organoplatinum Compounds
(adverse effects, pharmacology)
- Oxaliplatin
- Paclitaxel
(adverse effects, pharmacology)
- Rats
- Rats, Wistar
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