Phantip VattanaviboonNoppadol SiritanaratkulJidapa KetpirunePrapon WilairatYongyuth YuthavongMahidol UniversityFaculty of Medicine, Siriraj Hospital, Mahidol UniversityThailand National Science and Technology Development Agency2018-07-242018-07-242002-01-01Biochemical Pharmacology. Vol.64, No.1 (2002), 91-98000629522-s2.0-0036639486https://repository.li.mahidol.ac.th/handle/20.500.14594/20106Plasmodium falciparum infecting α-thalassemic erythrocytes are resistant to artemisinin and its derivatives. Binding of the drug to hemoglobin H resulting in drug inactivation was previously demonstrated. We now show that an additional host factor, membrane heme, significantly accounted for decreased antimalarial activity of artemisinin. The antimalarial activity of dihydroartemisinin in the presence of normal and thalassemic erythrocyte membranes showed a correlation with the heme content of the membrane (r2=0.466, P<0.01). The correlation was more clearly seen when the drug effectiveness was correlated with the heme content of α-thalassemic membrane (r2=0.636, P<0.01). However, the drug effectiveness showed no correlation to ferrozine-reactive (free or non-heme) iron content (r2=0.0001, P>0.05). α-Thalassemic erythrocytes contained higher amounts of membrane heme (11.04±8.96nmol/mg membrane protein) than those from normal and β-thalassemia/HbE erythrocytes (2.68±1.28 and 3.98±3.98nmol/mg membrane protein, respectively, P<0.01). Loss of drug effectiveness was also correlated with increment of heme content in membrane prepared from normal erythrocytes treated with phenylhydrazine. It is concluded that heme in both normal and thalassemic erythrocyte membranes is an important factor in drug inactivation. © 2002 Elsevier Science Inc. All rights reserved.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyPharmacology, Toxicology and PharmaceuticsArticleSCOPUS10.1016/S0006-2952(02)01060-2