IHEM   20887
INSTITUTO DE HISTOLOGIA Y EMBRIOLOGIA DE MENDOZA DR. MARIO H. BURGOS
Unidad Ejecutora - UE
artículos
Título:
Natural sesquiterpene lactones are active against Leishmania mexicana possible by multiple effects
Autor/es:
BARRERA P; JIMENEZ V; GIORDANO O; TONN C; GALANTI N; SOSA MA
Revista:
JOURNAL OF PARASITOLOGY
Editorial:
Allen Press
Referencias:
Año: 2008
ISSN:
0022-3395
Resumen:
In this paper, the effects of three natural sesquiterpene lactones - helenalin (Hln), mexicanin (Mxc) and dehydroleucodine (DhL) - were evaluated on cultured Leishmania mexicana promastigotes and it was observed that the compounds inhibited the in vitro growth of the parasites at relatively low concentrations. The effect was rapid and irreversible with an estimated IC50 2-4 ìM, while all the lactones were more effective than ketoconazole (IC50 12 ìM). Moreover, these compounds exhibited low cytotoxicity on mammalian cells. Hln induced strong vacuolization of the parasite cytoplasm, although pericellular microtubules were preserved. The three lactones induced DNA fragmentation as judged by the high labeling with the fluorescent TUNEL method, and confirmed by electrophoresis on agarose gels.  The ability of the parasites to invade Vero cells was also decreased by exposure to low concentrations of the compounds. We conclude that these compounds can affect the parasite life cycle, possibly through multiple mechanisms. Identification of the molecular targets of these natural products and studies of their effects on amastigotes should be carried out to evaluate the possible therapeutic use of the compounds against Leishmania.