Are currently deployed artemisinins neurotoxic?
In vitro, animal, and human clinical studies suggest currently deployed artemisinins possess neurotoxic potential. A specific and consistent pattern of brainstem injuries that includes auditory processing centers has been reported from all laboratory animals studied. Hearing loss, ataxia, and tremor are reported from humans. Neurotoxicity appears mediated in part through artemisinin induced oxidative stress in exposed brainstems. In vitro studies suggest that artemisinin neurotoxicity does not manifest immediately upon exposure, but that once commenced it is inevitable and irreversible; extrapolation from in vitro data suggests that 14 days may possibly be required for full development, casting doubt upon some animal safety studies and human necropsy studies. Uncertainty remains over the neurotoxicity of currently deployed artemisinins, and their safety profile should be reviewed, especially in pediatric use. The development of non-neurotoxic artemisinins is possible and should be encouraged.
Toovey
Stephen
S
Royal Free and University College Medical School, London, UK; Travel Clinic, Cape Town, South Africa. malaria@freesurf.ch
D000818:Animals; D000962:Antimalarials / Q000633:toxicity*; D037621:Artemisinins / Q000633:toxicity*; D001933:Brain Stem / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
D000962:Antimalarials; D037621:Artemisinins