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Neuropathologic toxicity of artemisinin derivatives in a mouse model.
Apichart Nontprasert
Apichart Nontprasert
Department of Clinical Tropical Medicine and Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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Sasithon Pukrittayakamee
Sasithon Pukrittayakamee
Department of Clinical Tropical Medicine and Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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Arjen M Dondorp
Arjen M Dondorp
Department of Clinical Tropical Medicine and Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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Ralf Clemens
Ralf Clemens
Department of Clinical Tropical Medicine and Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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Sornchai Looareesuwan
Sornchai Looareesuwan
Department of Clinical Tropical Medicine and Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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Nicholas J White
Nicholas J White
Department of Clinical Tropical Medicine and Bangkok Hospital for Tropical Diseases, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
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Intramuscular administration of high doses of artemether and arteether to experimental mammals produces selective damage to brain stem centers involved predominantly in auditory processing and vestibular reflexes. The relationship between clinical signs of neurotoxicity and neuropathologic toxicity was studied in the mouse. Intramuscular artemether (50-100 mg/kg/day for 28 days) caused dose-dependent neuropathologic damage to the brain stem. There was no pathologic evidence of neuronal death in mice receiving either oral artemether, or oral or intramuscular artesunate, in doses up to 300 mg/kg/day. The neurons in the lower brain stem trapezoid nucleus, the gigantocellular reticular nucleus, and the inferior cerebellar peduncle were the most sensitive to the toxic effects of artemether. All mice with neuropathologic changes also showed behavioral changes, whereas in some mice with gait disturbance, no corresponding histopathologic damage could be detected. Thus clinical assessment was a sensitive measure of neurotoxicity. There may be a reversible component to artemether neurotoxicity.
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| Past two years | Past Year | Past 30 Days | |
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