The metabonomic changes of leishmania major, s promastigotes (fredlin strain) after in vitro artemisinin treatment at stationary phase

Based on WHO classifications, leishmaniasis enumerates as one of the six important diseases in the tropics. It is also common in the Middle East and the Mediterranean countries. Control of the disease is important due to increased clinical cases in immune-system deficiency patients. With regard to the increasing need to new drugs with lesser side effects for the control and treatment of the disease, we surveyed the in vitro effects of artemisinin on the promastigotes of leishmania major, s metabolites in Pasteur institute of Iran. After IC50 determination, the effects of different concentrations of artemisinin drug were assessed on the metabolites of leishmania in two groups; the control group (without drug reception in culture media) and the case group (with drug reception in culture media), by using NMR technique. The results of this study indicate that in the metabolic changes in promastigotes of leishmania major (fredlin strain) at stationary phase, 5 metabolites of the 41 ones in the galactose metabolic cycle have shown significant changes. Therefore, galactose metabolism has changed the most, while sphingolipid, valine, leucine and isoleucine biosynthesis follow respectively. Artemisinin resulted in metabolic changes in biochemical pathways including galactose, sphingolipids and also valine, lucine, isoleucine that culminated in cessation of leishmania major’s (fredlin strain) activity. Spectra derived from H NMR showed significant difference (p<0.05) between metabolites of the drug received group and the non-drug received group. The identification of altered metabolic sites in these pathways could be used for the annihilation of the parasite. Thus, detecting the important genes for the parasite in these pathways, with high metabolic control over the parasite, but minimal control over the host, is needed. Considering the importance of leishmaniasis treatment and the present data about modified metabolism pathways, we could present a novel route for the future assessment of the disease, drug discovery and new treatment with more focus on these pathways