Document Detail


Implication of glutathione in the in vitro antiplasmodial mechanism of action of ellagic acid.
MedLine Citation:
PMID:  23029306     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The search for new antimalarial chemotherapy has become increasingly urgent due to parasite resistance to current drugs. Ellagic acid (EA) is a polyphenol, recently found in various plant products, that has effective antimalarial activity in vitro and in vivo without toxicity. To further understand the antimalarial mechanism of action of EA in vitro, we evaluated the effects of EA, ascorbic acid and N-acetyl-L-cysteine (NAC), alone and/or in combination on the production of reactive oxygen species (ROS) during the trophozoite and schizonte stages of the erythrocytic cycle of P. falciparum. The parasitized erythrocytes were pre-labelled with DCFDA (dichlorofluorescein diacetate). We showed that NAC had no effect on ROS production, contrary to ascorbic acid and EA, which considerably reduced ROS production. Surprisingly, EA reduced the production of the ROS with concentrations (6.6×10(-9) - 6.6×10(-6) M) ten-fold lower than ascorbic acid (113×10(-6) M). Additionally, the in vitro drug sensitivity of EA with antioxidants showed that antiplasmodial activity is independent of the ROS production inside parasites, which was confirmed by the additive activity of EA and desferrioxamine. Finally, EA could act by reducing the glutathione content inside the Plasmodium parasite. This was consolidated by the decrease in the antiplasmodial efficacy of EA in the murine model Plasmodium yoelii- high GSH strain, known for its high glutathione content. Given its low toxicity and now known mechanism of action, EA appears as a promising antiplasmodial compound.
Authors:
Patrice Njomnang Soh; Benoit Witkowski; Amandine Gales; Eric Huyghe; Antoine Berry; Bernard Pipy; Françoise Benoit-Vical
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-09-28
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-10-02     Completed Date:  2013-02-28     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e45906     Citation Subset:  IM    
Affiliation:
CNRS, Laboratoire de Chimie de Coordination (LCC), Toulouse, France. sohnjomnang@yahoo.fr
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MeSH Terms
Descriptor/Qualifier:
Acetylcysteine / pharmacology
Animals
Antimalarials / pharmacology*
Antioxidants / metabolism,  pharmacology*,  physiology
Ascorbic Acid / pharmacology
Buthionine Sulfoximine / pharmacology
Cells, Cultured
Deferoxamine / pharmacology
Drug Synergism
Ellagic Acid / pharmacology*
Enzyme Inhibitors / pharmacology
Erythrocytes / drug effects,  metabolism,  parasitology
Glutathione / metabolism,  pharmacology,  physiology*
Humans
Inhibitory Concentration 50
Mice
Oxidation-Reduction
Plasmodium falciparum / drug effects*,  growth & development,  metabolism
Plasmodium yoelii / drug effects
Reactive Oxygen Species
Siderophores / pharmacology
Chemical
Reg. No./Substance:
0/Antimalarials; 0/Antioxidants; 0/Enzyme Inhibitors; 0/Reactive Oxygen Species; 0/Siderophores; 476-66-4/Ellagic Acid; 50-81-7/Ascorbic Acid; 5072-26-4/Buthionine Sulfoximine; 616-91-1/Acetylcysteine; 70-18-8/Glutathione; 70-51-9/Deferoxamine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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