| Iron-dependent free radical generation from the antimalarial agent artemisinin (qinghaosu). | |
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MedLine Citation:
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PMID: 8517699 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Artemisinin is an important new antimalarial agent containing a bridged endoperoxide. The in vitro antimalarial activity of an artemisinin derivative, arteether, is antagonized by two iron chelators, pyridoxal benzoylhydrazone and 1,2-dimethyl-3-hydroxypyrid-4-one. Similarly, the acute toxicity of artemisinin in mice is antagonized by another chelator, deferoxamine-hydroxyethylstarch. A combination of artemisinin and hemin oxidizes erythrocyte membrane thiols in vitro, and this oxidation is also inhibited by an iron chelator. Thus, iron plays a role in the mechanisms of action and toxicity of artemisinin. The combination of artemisinin and hemin also decreases erythrocyte deformability. Iron probably catalyzes the generation of free radicals from artemisinin since alpha-tocopherol antagonizes the thiol-oxidizing activity of artemisinin and since a spin-trapped free radical signal can be seen by electron paramagnetic resonance only when artemisinin is incubated in the presence of iron. |
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Authors:
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S R Meshnick; Y Z Yang; V Lima; F Kuypers; S Kamchonwongpaisan; Y Yuthavong |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Antimicrobial agents and chemotherapy Volume: 37 ISSN: 0066-4804 ISO Abbreviation: Antimicrob. Agents Chemother. Publication Date: 1993 May |
Date Detail:
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Created Date: 1993-07-22 Completed Date: 1993-07-22 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 0315061 Medline TA: Antimicrob Agents Chemother Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 1108-14 Citation Subset: IM |
Affiliation:
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Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor 48109. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antimalarials / antagonists & inhibitors, pharmacology*, therapeutic use Artemisinins* Drugs, Chinese Herbal / pharmacology* Erythrocyte Deformability / drug effects Free Radicals / metabolism Iron / metabolism* Iron Chelating Agents / pharmacology Malaria, Falciparum / drug therapy, parasitology Male Mice Plasmodium falciparum / drug effects Sesquiterpenes / antagonists & inhibitors, pharmacology*, therapeutic use |
| Grant Support | |
ID/Acronym/Agency:
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AI26848/AI/NIAID NIH HHS; DK92111/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antimalarials; 0/Artemisinins; 0/Drugs, Chinese Herbal; 0/Free Radicals; 0/Iron Chelating Agents; 0/Sesquiterpenes; 63968-64-9/artemisinine; 7439-89-6/Iron |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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