Extracellular Heme Enhances the Antimalarial Activity of Artemisinin

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概要

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• Artemisinin exerts the antimalarial activity through activation by heme. The hemolysis in malaria results in the elevated levels of plasma heme which may affect the activity of artemisinin. We hypothesized that the extracellular heme would potentiate the antimalarial activity of artemisinin. Hemin (ferric heme) at the pathologic concentrations enhanced the activity of artemisinin against Plasmodium falciparum in vitro and increased the levels of the lipid peroxidation products in the presence of artemisinin. The antimalarial activity of artemisinin and potentiation by hemin was decreased by vitamin E. Hemin had no effect on the activity of quinoline drugs (chloroquine, quinine and mefloquine). Furthermore, the oxidative effect of hemin in the presence of artemisinin or quinoline drugs was studied using low-density lipoprotein (LDL) oxidation as a model. Artemisinin enhanced the effects of hemin on lipid peroxidation and a decrease of tryptophan fluorescence in LDL whereas the quinoline drugs inhibited the oxidation by hemin. In conclusion, the extracellular hemin enhances the antimalarial activity of artemisinin as a result of the increasing oxidative effect of hemin.

著者

• Udomsangpetch Rachanee

  Department Of Pathobiology Faculty Of Science Mahidol University

• SIBMOOH Nathawut

  Department of Pharmacology, Faculty of Science, Mahidol University

• Unchern Supeenun

  Department Of Pharmacology Faculty Of Science Mahidol University

• Tangnitipong Sunanta

  Department of Pharmacology, Faculty of Science, Mahidol University

• Thaptimthong Thitiporn

  Department of Pharmacology, Faculty of Science, Mahidol University

• Srihirun Sirada

  Department of Pharmacology, Faculty of Science, Mahidol University

• Kittikool Dusadee

  Department of Pharmacology, Faculty of Science, Mahidol University

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