Articles written in Journal of Biosciences
Volume 42 Issue 3 September 2017 pp 427-438 Article
Leishmania establishes a successful parasitism by evading both oxidative and non-oxidative killing pathways, and its drugresistance against the currently available therapeutics demands for a safe and cheap drug. Since the parasite synthesizesergosterol instead of cholesterol, using the same biochemical pathway and enzymes, an inhibitor of HMG-CoA-Reductase,Lovastatin, has been tried for its anti-Leishmanial effect. Lovastatin, being an inhibitor of HMG-CoA-Reductase, inhibitsinfection by cholesterol depletion, while chromium chloride complexes, at their higher concentrations, are reported toexhibit cytotoxicity. In intracellular amastigotes, cytotoxicity has been checked by assessing various manifestation of celldeath, viz. DNA fragmentation, AnnexinV-FITC binding and JC-1 fluorescence ratio. Release of hydrogen peroxide (HPO)and nitric oxide (NO) has been assessed in live cell. Lovastatin and CrCl3.6H2O in combination has appeared to beineffective on promastigotes but has induced cytotoxic effect on the intracellular amastigotes through up-regulation ofcellular signalling mechanisms. CrCl3.6H2O stimulates generation of NO, leading to reduction of the number of intracellularamastigote, while Lovastatin shows HPO-mediated killing of the same, keeping the host cell unaffected. This noveltherapeutic approach, involving two known safe compounds in suboptimal doses, may resolve human visceralLeishmaniasis.
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