Evaluation of misonidazole peripheral neurotoxicity in rats by analysis of nerve trains evoked response.
The clinical use of misonidazole and other nitroimidazole radiosensitizing agents is limited by the peripheral and central neurotoxicity that is produced in animals and humans. In a blinded study, rats treated with misonidazole at either 100 mg/kg or 300 mg/kg, 5 days/week for 3 weeks, were evaluated for peripheral neurotoxicity using nerve trains evoked responses. Only one rat treated at a dose of 100 mg/kg developed symptoms and signs of neurotoxicity, while all rats treated at 300 mg/kg developed these signs and symptoms. Nerve trains analysis made possible a diagnosis of neurotoxicity before overt clinical signs appeared. This test is non-invasive and may be useful for evaluating patients receiving nitroimidazole radiosensitizers as part of a radiation therapy regimen.
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D005071:Evoked Potentials / Q000187:drug effects; D008920:Misonidazole / Q000008:administration & dosage / Q000633:toxicity; D008991:Monitoring, Physiologic / Q000379:methods*; D010525:Peripheral Nerves / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000503:physiopathology; D010865:Pilot Projects; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D011838:Radiation-Sensitizing Agents; D008920:Misonidazole