دورية أكاديمية
Dose effects of oxaliplatin on persistent and transient Na+ conductances and the development of neurotoxicity.
| العنوان: | Dose effects of oxaliplatin on persistent and transient Na+ conductances and the development of neurotoxicity. |
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| المؤلفون: | Susanna B Park, Cindy S-Y Lin, Arun V Krishnan, David Goldstein, Michael L Friedlander, Matthew C Kiernan |
| المصدر: | PLoS ONE, Vol 6, Iss 4, p e18469 (2011) |
| بيانات النشر: | Public Library of Science (PLoS) |
| سنة النشر: | 2011 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | BACKGROUND: Oxaliplatin, a platinum-based chemotherapy utilised in the treatment of colorectal cancer, produces two forms of neurotoxicity--acute sensorimotor neuropathic symptoms and a dose-limiting chronic sensory neuropathy. Given that a Na(+) channelopathy has been proposed as the mechanism underlying acute oxaliplatin-induced neuropathy, the present study aimed to determine specific mechanisms of Na(+) channel dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: Specifically the function of transient and persistent Na(+) currents were followed during treatment and were investigated in relation to oxaliplatin dose level. Eighteen patients were assessed before and after a single oxaliplatin infusion with motor and sensory axonal excitability studies performed on the median nerve at the wrist. While refractoriness (associated with Na(+) channel inactivation) was significantly altered post-oxaliplatin infusion in both motor (Pre: 31.7±6.4%; Post: 68.8±14.5%; P≤.001) and sensory axons (Pre: 31.4±5.4%; Post: 21.4±5.5%; P<.05), strength-duration time constant (marker of persistent Na(+) conductances) was not significantly altered post-infusion (Motor Pre: 0.395±0.01 ms; Post: 0.394±0.02 ms; NS; Sensory Pre:0.544±0.03 ms; Post: 0.535±0.05 ms; NS). However, changes in strength-duration time constant were significantly correlated with changes in refractoriness in motor and sensory axons (Motor correlation coefficient = -.65; P<.05; Sensory correlation coefficient = .67; P<.05). CONCLUSIONS/SIGNIFICANCE: It is concluded that the predominant effect of acute oxaliplatin exposure in human motor and sensory axons is mediated through changes in transient rather than persistent Na(+) conductances. These findings are likely to have implications for the design and trial of neuroprotective strategies. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1932-6203 |
| العلاقة: | http://europepmc.org/articles/PMC3072981?pdf=renderTest; https://doaj.org/toc/1932-6203Test; https://doaj.org/article/0d118f65c827480a96fa716acc239d84Test |
| DOI: | 10.1371/journal.pone.0018469 |
| الإتاحة: | https://doi.org/10.1371/journal.pone.0018469Test https://doaj.org/article/0d118f65c827480a96fa716acc239d84Test |
| رقم الانضمام: | edsbas.70BC314A |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 19326203 |
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| DOI: | 10.1371/journal.pone.0018469 |