Abstract
The antimalarial drug artemisinin and its derivatives display neurotoxicity in animal studies in vivo and in neuronal cells in vitro. Their toxicity may be due to an interaction of iron with the endoperoxide bridge of the derivative to produce toxic free radicals and/or other toxic metabolites. In this study, 0.3 microM artemether (AEM) in the presence of 2 microM haemin significantly inhibited the outgrowth of neurites from differentiating NB2a neuroblastoma cells by up to 76%. The antioxidants ascorbic acid and glutathione completely protected against this toxicity at a concentration of 100 microM. AEM was found to be partially converted to two isomeric products, which were identified as the tetrahydrofuran acetate isomer of AEM and 3alpha-hydroxydesoxyartemether.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antimalarials / toxicity*
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Artemether
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Artemisinins*
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Ascorbic Acid / pharmacology
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Brain Neoplasms / chemically induced
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Brain Neoplasms / pathology
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Cell Differentiation / drug effects
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Culture Media
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Glutathione / pharmacology
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Hemin / metabolism
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Iron / physiology*
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Mice
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Nervous System Diseases / chemically induced*
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Nervous System Diseases / pathology
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Neurites / drug effects
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Neurites / ultrastructure
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Neuroblastoma / chemically induced
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Neuroblastoma / pathology
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Neurotoxins / toxicity*
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Sesquiterpenes / metabolism
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Sesquiterpenes / toxicity*
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Tumor Cells, Cultured
Substances
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Antimalarials
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Artemisinins
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Culture Media
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Neurotoxins
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Sesquiterpenes
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Hemin
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artemisinin
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Artemether
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Iron
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Glutathione
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Ascorbic Acid