1887

Abstract

Leishmaniasis constitutes a complex of diseases with clinical and epidemiological diversity and includes visceral leishmaniasis, a disease that is fatal when left untreated. In earlier studies, the authors reported that leaf exudate (AVL) is a potent antileishmanial agent effective in promastigotes of ,,, and and also in axenic amastigotes of . In the present study, it has been demonstrated that, in promastigotes of (IC=110 μg ml), AVL mediates this leishmanicidal effect by triggering a programmed cell death. Incubation of promastigotes with AVL caused translocation of phosphatidylserine to the outer leaflet of the plasma membrane as measured by annexin V binding, which was accompanied by loss of mitochondrial membrane potential, release of cytochrome into the cytosol and concomitant nuclear alterations that included chromatin condensation, deoxynucleotidyltransferase-mediated dUTP end labelling and DNA laddering. As this AVL-induced leishmanicidal effect could not be inhibited by protease inhibitors including Z-Val-Ala--Asp (methoxy)-fluoromethylketone, a broad-spectrum caspase inhibitor, non-involvement of caspases and major proteases was suggested. Additionally, AVL treatment caused no increase in cytosolic Ca or generation of reactive oxygen species, indicating that although promastigote death was induced by an apoptotic-like mechanism similar to metazoan apoptosis, the pathways of induction and/or execution differed at the molecular level.

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2007-05-01
2019-10-21
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