| Iron enhances generation of free radicals by Artemisinin causing a caspase-independent, apoptotic death in Leishmania donovani promastigotes. | |
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MedLine Citation:
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PMID: 20815780 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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An increasing incidence of unresponsiveness to antimonials in Leishmaniasis has led to identification of plant-derived anti-leishmanial compounds like Artemisinin. Since iron-mediated generation of free radicals sustains the anti-malarial activity of Artemisinin, this study investigated whether similar mechanisms accounted for its activity in Leishmania promastigotes. Artemisinin effectively disrupted the redox potential via an increased generation of free radicals along with a decrease in levels of non-protein thiols. Attenuation of its IC50 by a free radical scavenger N-acetyl L-cysteine and an iron chelator desferoxamine established the pivotal role of free radicals and of the potentiating effect of iron. An enhanced Fluo-4 fluorescence reflected Artemisinin-induced mobilization of intracellular calcium, which triggered apoptosis. However, the absence of any detectable caspase activity indicated that the leishmanicidal activity of Artemisinin is mediated by an iron-dependent generation of reactive intermediates, terminating in a caspase-independent, apoptotic mode of cell death. |
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Authors:
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Rupashree Sen; Piu Saha; Avijit Sarkar; Sudipto Ganguly; Mitali Chatterjee |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Free radical research Volume: 44 ISSN: 1029-2470 ISO Abbreviation: Free Radic. Res. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-10-14 Completed Date: 2011-01-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9423872 Medline TA: Free Radic Res Country: England |
Other Details:
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Languages: eng Pagination: 1289-95 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Institute of Post Graduate Medical Education and Research, 244 B, Acharya J C Bose Road, Kolkata 700 020, India. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Anti-Infective Agents
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pharmacology* Apoptosis / drug effects* Artemisinins / pharmacology* Caspases / metabolism Free Radicals / metabolism Humans Iron / pharmacology* Leishmania donovani / drug effects*, metabolism Leishmaniasis / drug therapy Reactive Oxygen Species / metabolism U937 Cells |
| Chemical | |
Reg. No./Substance:
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0/Anti-Infective Agents; 0/Artemisinins; 0/Free Radicals; 0/Reactive Oxygen Species; 63968-64-9/artemisinine; 7439-89-6/Iron; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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