In Vitro and In Vivo Studies of Antileishmanial Effect of Artemether on Leishmania infantum

Abstract

Background: Visceral leishmaniasis is the most acute form of leishmaniasis. Instead of administering usual drugs with different side effects, applying a herbal drug can put forward a novel horizon in dealing with this parasite. Artemether is one of the derivatives of artemisinin, a new anti-malarial drug, and can be activated by heme to produce free radicals which, in turn, have toxic effect on the parasite. Objectives: In this study we used artemether as a new drug for treatment of visceral leishmaniasis. Materials and Methods: In the present study, BALB/c mice infected with Leishmania infantum (MHOM/TN/80/IPI1) were treated with the most effective dose of artemether assessed with In Vitro assay. Artemether was given in parenteral and oral forms. Parasite burdens in the spleen and liver were determined by homogenizing and counting the parasite rate and were compared with those in the untreated mice. To evaluate the apoptotic properties of artemether by FACS flowcytometry, annexin-V FLUOS staining was performe. Results: IC50 of the drug on Leishmania infantum was determined to be 25 μg/mL after 24 h. In Vivo experiments indicated that oral artemether treatment of mice, during 3 days and every 6 h (0.625 mg/kg) was more significant than parenteral (0.625 mg/kg IP) treatment. Artemether exerts its cytotoxic effect on this parasite via apoptosis-related mechanism. Accordingly, parasite burden in the current study decreased in the liver and spleen of mice by oral treatment. Conclusions: Artemether especially in oral treatment is an effective and simple method and may be used as a new method to treat visceral leishmaniasis.