Annals of Tropical Medicine and Public Health
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ORIGINAL ARTICLE
Year : 2009  |  Volume : 2  |  Issue : 2  |  Page : 37-41

Artesunate opens mitochondrial membrane permeability transition pore


1 Department of Basic & Applied Sciences, Babcock University, Ilisan-Remo, Ogun state, Nigeria
2 Laboratories for Biomembrane Research & Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Nigeria

Correspondence Address:
O O Olorunsogo
Laboratories for Biomembrane Research & Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan
Nigeria
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Source of Support: None, Conflict of Interest: None


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The incidence of malaria is dramatically increasing, especially because parasites responsible for the majority of fatal malaria infections have now become resistant to commonly used antimalarial drugs such as chloroquine, mefloquine, and quinine. To combat this menace, the World Health Organization (WHO) introduced a new antimalarial drug called artesunate; a hemi-succinate derivative of artemisinin. The in vivo effects of artesunate on rat liver mitochondrial membrane permeability transition (MMPT) pore were investigated in Wister strain albino rats exposed to various doses of artesunate (1.5, 2.0, 3.0 and 5.0 mg per kg body weight per day) for five days. Membrane permeability transition was estimated under energized and de energized spectrophotometric method of Lapidus and Sokolove. The results revealed that artesunate tested at the various doses induced mitochondrial pore opening, induction being minimal (68%) at 5 mg/kg and maximal (240%) at 1.5 mg/kg. In vitro, artesunate at 30, 50 and 70 mg/ml also had an inductive effect in a concentration-dependent manner with minimum induction (18.1%) at 30 mg/ml and maximum induction (32.7%) at 70 mg/ml. Further, preincubation of mitochondria with artesunate for five minutes caused an induction of pore opening in a concentration-dependent manner, with minimum induction (7.9%) at 10 mg/ml and maximum induction (48.6%) at 70 mg/ml. In conclusion, these findings indicate that artesunate could be cytotoxic, opening mitochondrial membrane permeability transition pore, causing the release of cytochrome c and eventually apoptosis.


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