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Published on: January 29, 2018
Peripheral electrophysiological parameters in mice treated with misonidazole
Abstract:
The clinical use of the radiosensitizer misonidazole may be limited by the incidence of peripheral neuropathy reported following total doses in excess of 18 g. A recent report noted a decrease in nerve conduction velocity following a single i.p. injection of 1 mg/g misonidazole in mice. The present study was unable to confirm such changes when nerve conduction velocity measurements were made in situ or in isolated sural, tibial or median nerves of mice. Other electrophysiological parameters such as threshold, strength-duration curves, refractory time or the ability to carry high-frequency stimulation also showed no change. However, it was noted that a single administration of the radio-sensitizer produced a marked decrease in body temperature which persisted for at least 2 h after the elimination of the drug from the blood serum. The physiological response of reduction of body temperature may protect the mouse against the effect of the toxic chemical species involved in the induction of neurotoxicity.
Insights
Misonidazole, a radiosensitizer, did not affect nerve conduction velocity in mice. However, it caused a significant drop in body temperature, potentially protecting against neurotoxicity.
Area of Science:
- Neuroscience
- Pharmacology
- Radiotherapy
Background:
- Clinical use of misonidazole is limited by peripheral neuropathy.
- Previous studies suggested misonidazole reduces nerve conduction velocity.
Purpose of the Study:
- To investigate the neurotoxic effects of misonidazole on nerve electrophysiology.
- To determine if misonidazole affects nerve conduction velocity in mice.
Main Methods:
- In situ and isolated nerve electrophysiological measurements in mice.
- Assessed nerve conduction velocity, threshold, strength-duration curves, and refractory time.
- Monitored body temperature and misonidazole serum levels.
Main Results:
- Misonidazole did not alter nerve conduction velocity or other electrophysiological parameters.
- A single dose of misonidazole caused a significant decrease in body temperature.
- This hypothermic effect persisted for at least 2 hours post-administration.
Conclusions:
- Misonidazole does not appear to cause acute neurotoxicity affecting nerve conduction velocity in mice.
- The observed hypothermia may be a protective mechanism against misonidazole-induced neurotoxicity.
