Inactivation of artemisinin by thalassemic erythrocytes

• Published in: Biochemical pharmacology 2000-06, Vol.59 (11), p.1337-1344
• Main Authors: Charoenteeraboon, Juree, Kamchonwongpaisan, Sumalee, Wilairat, Prapon, Vattanaviboon, Phantip, Yuthavong, Yongyuth
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antimalarials - antagonists & inhibitors; Antimalarials - metabolism; Antimalarials - pharmacology; Antiparasitic agents; artemisinin; artemisinin inactivation; Artemisinins; Biological and medical sciences; Cell Membrane - metabolism; Cytosol - metabolism; Drug Resistance; erythrocytes; Erythrocytes - metabolism; Hemoglobin H - metabolism; Humans; In Vitro Techniques; malaria; Medical sciences; Pharmacology. Drug treatments; Plasmodium falciparum; Plasmodium falciparum - drug effects; Protective Agents - pharmacology; Serum Albumin - pharmacology; Sesquiterpenes - antagonists & inhibitors; Sesquiterpenes - metabolism; Sesquiterpenes - pharmacology; thalassemia; Thalassemia - blood; Thalassemia - metabolism
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/S0006-2952(00)00271-9

Plasmodium falciparum infecting α-thalassemic erythrocytes (Hb H or Hb H/Hb Constant Spring) is resistant to artemisinin derivatives. Similar resistance, albeit at a much lower level, is shown by the parasite infecting β-thalassemia/Hb E erythrocytes. The resistance is due to host-specific factors, one of which is the higher uptake of the drugs by thalassemic erythrocytes than normal erythrocytes, due to binding with Hb H. In addition to higher drug binding, incubation of artemisinin with α-thalassemic erythrocytes resulted in preferential inactivation of the drug. Both thalassemic and normal erythrocytes have the capability to inactivate the drug. Addition of serum can protect against inactivation by normal erythrocytes, but not by thalassemic erythrocytes. Incubation with either the hemolysate or the membrane fraction from these erythrocytes also resulted in preferential inactivation of the drug. The drug was also inactivated by purified Hb H. It is concluded that the ineffectiveness of artemisinin derivatives against P. falciparum infecting thalassemic erythrocytes is due partly to competition of the host cell components for binding with the drugs, and partly to inactivation of the drugs by the cell components.