Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1997-3-28
pubmed:abstractText
Despite the wide use of artermisinin and its derivatives, concerns have been raised about their potential neurotoxicity. Accordingly, studies were undertaken on rats treated with high doses of arteether and on mouse neuroblastoma cells (Neu2a) treated with 3H-dihydroartemisinin. Rats uniformly developed neurologic symptoms following intramuscular administration of 50 mg/kg/day of arteether for 5-6 days. Acute neuronal necrosis associated with vacuolization and focal axonal swelling in the neuropil was observed in specific areas of the brain, especially the vestibular nuclei and red nuclei. Scattered swollen neurons were also evident in the cerebellar nuclei and the reticular formation. No neurologic symptoms, neuronal nuclei necrosis, nor gliosis was observed in rats administered 25 or 30 mg/kg/day for six or eight days. In vitro, Neu2a cells took up much less 3H-dihydroartemisinin than Plasmodium falciparum-infected red blood cells when incubated under identical conditions for 4 hr with 4.2 microM 3H-dihydroartemisinin. This selective uptake may explain why the artemisinin derivatives are selectively toxic to malaria parasites. Autoradiograms of sodium dodecyl sulfate-polyacrylamide gels run from 3H-dihydroartemisinin-treated cells showed that neuronal proteins with molecular weights of 27, 32, 40, and 81 kD were alkylated, although not nearly as strongly or rapidly as the P. falciparum proteins. The results indicate that while artemisinin derivatives have neurotoxic effects in rats and alkylate proteins in neuroblastoma cells, these effects only occur at high doses or after prolonged exposure.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0002-9637
pubmed:author
pubmed:issnType
Print
pubmed:volume
56
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7-12
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:9063352-Alkylation, pubmed-meshheading:9063352-Animals, pubmed-meshheading:9063352-Antimalarials, pubmed-meshheading:9063352-Artemisinins, pubmed-meshheading:9063352-Blood Proteins, pubmed-meshheading:9063352-Brain, pubmed-meshheading:9063352-Detergents, pubmed-meshheading:9063352-Erythrocytes, pubmed-meshheading:9063352-Male, pubmed-meshheading:9063352-Mice, pubmed-meshheading:9063352-Molecular Weight, pubmed-meshheading:9063352-Nerve Tissue Proteins, pubmed-meshheading:9063352-Neuroblastoma, pubmed-meshheading:9063352-Neurons, pubmed-meshheading:9063352-Octoxynol, pubmed-meshheading:9063352-Plasmodium falciparum, pubmed-meshheading:9063352-Rats, pubmed-meshheading:9063352-Rats, Sprague-Dawley, pubmed-meshheading:9063352-Sesquiterpenes, pubmed-meshheading:9063352-Tumor Cells, Cultured
pubmed:year
1997
pubmed:articleTitle
Artemisinin neurotoxicity: neuropathology in rats and mechanistic studies in vitro.
pubmed:affiliation
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't