Publication: Artemisinin effectiveness in erythrocytes is reduced by heme and heme-containing proteins
Issued Date
2007-06-30
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ISSN
00062952
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2-s2.0-34249323755
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Mahidol University
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SCOPUS
Bibliographic Citation
Biochemical Pharmacology. Vol.74, No.1 (2007), 153-160
Suggested Citation
Napawan Ponmee, Tatsanee Chuchue, Prapon Wilairat, Yongyuth Yuthavong, Sumalee Kamchonwongpaisan Artemisinin effectiveness in erythrocytes is reduced by heme and heme-containing proteins. Biochemical Pharmacology. Vol.74, No.1 (2007), 153-160. doi:10.1016/j.bcp.2007.03.008 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/24180
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Title
Artemisinin effectiveness in erythrocytes is reduced by heme and heme-containing proteins
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Abstract
Artemisinin loses its antimalarial activity on prolonged exposure to erythrocytes, especially α-thalassemic erythrocytes. In this report, we show that the major artemisinin-inactivating factor in cytosol of normal erythrocytes was heat-labile but a heat-stable factor from α-thalassemic cells also played a significant role in reducing artemisinin effectiveness, which was shown to be heme released from hemoglobin (Hb). Studies of fractionated lysate from genetically normal erythrocytes revealed that the protein fraction with molecular weight greater than 100 kDa was capable of reducing artemisinin effectiveness more readily than lower molecular weight fraction. Catalase and Hb A, but not selenoprotein glutathione peroxidase, were capable of reducing artemisinin effectiveness. Hemin (ferriprotoporphyrin IX) also reduced artemisinin effectiveness in a concentration- and time-dependent manner. It is concluded that heme and heme-containing proteins in erythrocyte are largely responsible for reducing artemisinin effectiveness and may contribute to resistance of Plasmodium falciparum infecting α-thalassemic erythrocytes observed in vitro. © 2007 Elsevier Inc. All rights reserved.