Oxaliplatin-induced hyperexcitation of rat sciatic nerve fibers: an intra-axonal study.
Τίτλος | Oxaliplatin-induced hyperexcitation of rat sciatic nerve fibers: an intra-axonal study. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Kagiava, A., Kosmidis E. K., & Theophilidis G. |
Journal | Anticancer Agents Med Chem |
Volume | 13 |
Issue | 2 |
Pagination | 373-9 |
Date Published | 2013 Feb |
ISSN | 1875-5992 |
Λέξεις κλειδιά | Animals, Axons, Dose-Response Relationship, Drug, Male, Nerve Fibers, Organoplatinum Compounds, Potassium Channels, Voltage-Gated, Rats, Rats, Wistar, Sciatic Nerve, Structure-Activity Relationship, Time Factors |
Abstract | Oxaliplatin is an agent that is used extensively in gastrointestinal cancer chemotherapy. The agent's major dose-limiting toxicity is peripheral neuropathy that can manifest as a chronic or an acute syndrome. Oxaliplatin-induced acute neuropathy is purportedly caused by an alteration of the biophysical properties of voltage-gated sodium channels. However, sodium channel blockers have not been successful at preventing acute neuropathy in the clinical setting. We report intra-axonal recordings from the isolated rat sciatic nerve preparation under the effect of oxaliplatin. The depolarization phase of single action potentials remains intact with a duration of 0.52 ± 0.02 ms (n=68) before and 0.55 ± 0.01 ms (n=68) after 1-5 h of exposure to 150 μM oxaliplatin (unpaired t-test, P > 0.05) whereas there is a significant broadening of the repolarization phase (2.16 ± 0.10 ms, n=68, before and 5.90 ± 0.32 ms after, n=68, unpaired t-test, P < 0.05). Apart from changes in spike shape, oxaliplatin also had drastic concentration- and time-dependent effects on the firing responses of fibers to short stimuli. In the intra-axonal recordings, three groups of firing patterns were indentified. The first group shows bursting (internal frequency 90 - 130 Hz, n=88), the second shows a characteristic plateau (at -19.27�2.84 mV, n=31, with durations ranging from 45 - 140 ms depending on the exposure time), and the third combines a plateau and a bursting period. Our results implicate the voltage-gated potassium channels as additional oxaliplatin targets, opening up new perspectives for the pharmacological prevention of peripheral neuropathy. |
Alternate Journal | Anticancer Agents Med Chem |
PubMed ID | 22721389 |