Journal
JOURNAL OF BIOSCIENCES
Volume 42, Issue 3, Pages 427-438Publisher
INDIAN ACAD SCIENCES
DOI: 10.1007/s12038-017-9690-9
Keywords
Chromium chloride hexahydrate (CrCl3 center dot 6H(2)O); hydrogen peroxide (HPO); Lovastatin; mitochondrial membrane potential (MMP); nitric oxide (NO); nucleosomal DNA fragmentation; reactive oxygen species; visceral Leishmaniasis
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Funding
- Department of Biotechnology (DBT), India [BT/PR15025/GBD/27/284/2010]
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Leishmania establishes a successful parasitism by evading both oxidative and non-oxidative killing pathways, and its drug resistance against the currently available therapeutics demands for a safe and cheap drug. Since the parasite synthesizes ergosterol 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, inhibits infection by cholesterol depletion, while chromium chloride complexes, at their higher concentrations, are reported to exhibit cytotoxicity. In intracellular amastigotes, cytotoxicity has been checked by assessing various manifestation of cell death, 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 center dot 6H(2)O in combination has appeared to be ineffective on promastigotes but has induced cytotoxic effect on the intracellular amastigotes through up-regulation of cellular signalling mechanisms. CrCl3 center dot 6H(2)O stimulates generation of NO, leading to reduction of the number of intracellular amastigote, while Lovastatin shows HPO-mediated killing of the same, keeping the host cell unaffected. This novel therapeutic approach, involving two known safe compounds in suboptimal doses, may resolve human visceral Leishmaniasis.
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