Napawan PonmeeTatsanee ChuchuePrapon WilairatYongyuth YuthavongSumalee KamchonwongpaisanThailand National Center for Genetic Engineering and BiotechnologyMahidol University2018-08-242018-08-242007-06-30Biochemical Pharmacology. Vol.74, No.1 (2007), 153-160000629522-s2.0-34249323755https://repository.li.mahidol.ac.th/handle/123456789/24180Artemisinin 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.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1016/j.bcp.2007.03.008