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Evoked potentials in rats with misonidazole neurotoxicity. I. Brain stem auditory evoked potentials
Abstract:
Central neurotoxicity produced in rats by daily administration of 300 mg/kg of misonidazole (MISO) 5 times/week for 4-5 weeks (total dose = 6.0 gm/kg) was evaluated weekly wit brain stem auditory evoked potentials (BAEPs). Compared to untreated control rats, all treated rats had a prolongation of the I-IV interpeak latency (p less than 0.005) at a mean of 13.2 +/- 2.7 days at a cumulative dose of approximately 4.0 gm/kg of MISO per rat. In some rats, the I-III and I-II interwave latencies were prolonged and waves III and IV were lost. Control rats did not show any significant alteration in BAEP latency or amplitude. Histopathologic examination of the brain stems of treated rats showed that necrotic lesions were present primarily in the nuclei of the tegmentum of the fourth ventricle, with scattered nuclear involvement in the cerebellar roof nuclei, inferior olive, and nucleus of the spinal tract of the trigeminal nerve. The cerebral cortex appeared to be normal in all treated rats. Changes in BAEPs caused by central neurotoxicity correlated with the histopathologic findings. We conclude that BAEPs are a sensitive method for evaluating MISO central neurotoxicity in the rat model.
Insights
Misonidazole (MISO) causes central neurotoxicity in rats, evidenced by prolonged brainstem auditory evoked potentials (BAEPs) and histopathological lesions. BAEPs are a sensitive indicator for MISO neurotoxicity.
Area of Science:
- Neuroscience
- Toxicology
- Pharmacology
Background:
- Misonidazole (MISO) is a hypoxic cell radiosensitizer used in cancer therapy.
- Central neurotoxicity is a potential adverse effect of MISO treatment.
- Early detection of MISO-induced neurotoxicity is crucial for patient safety.
Purpose of the Study:
- To evaluate the efficacy of brainstem auditory evoked potentials (BAEPs) in detecting central neurotoxicity induced by MISO in a rat model.
- To correlate BAEP changes with histopathological findings in the brainstem.
Main Methods:
- Rats were administered MISO (300 mg/kg) daily, 5 times/week for 4-5 weeks.
- BAEPs were recorded weekly to assess neurotoxicity.
- Histopathological examination of brainstems was performed post-treatment.
Main Results:
- All MISO-treated rats exhibited prolonged I-IV interpeak latency in BAEPs, starting around a cumulative dose of 4.0 gm/kg.
- Some rats showed prolonged I-III and I-II interwave latencies, with loss of waves III and IV.
- Histopathology revealed necrotic lesions in the brainstem tegmentum, correlating with BAEP alterations.
Conclusions:
- BAEPs are a sensitive and reliable method for monitoring MISO-induced central neurotoxicity in rats.
- The study demonstrates a correlation between electrophysiological changes (BAEPs) and neuropathological findings.
- This suggests BAEPs could be a valuable tool for early detection and management of MISO neurotoxicity.