Antiproliferative and leishmanicidal effect of ajoene on various Leishmania species: ultrastructural study.
Ajoene [(E,Z)-4,5,9 trithiadodeca 1,6,11 triene 9-oxide], the major bioactive compound derived from garlic, shows a potent trypanolytic and antimicotic activity. In this paper we evaluate its effect on Leishmania mexicana(Lm:MHOM/VE/80/NR), L eishmania mexicana venezuelensis (Lmv: MHOM/VE/80/H16), L eishmania mexicana amazonensis (Lma: M112, IFLA/BR/67/PH8) and L eishmania donovani chagasi (Ldch: MHOM/BR/74/PP75). Ajoene showed a potent leishmanicidal activity in vitro against all species studied. Concentrations higher than 0.3 microM led to total inhibition of growth, and 10 microM induced 100% lysis of Leishmaniaafter 96 h of incubation in a chemically defined culture medium. The 50% inhibitory concentration (IC(50)) for lysis, for all species, was about to 2 microM. The effect was dose-dependent and a threefold increase in concentration (30 microM) produced 100% lysis of cultured forms after 72 h. Ultrastructural studies showed a time- and dose-dependent morphological alteration of the mitochondrial membrane and nuclear envelope, as well as the formation of large autophagic vacuoles.
Universidad de Oriente, Centro de Investigaciones en Ciencias de la Salud (CICS), Instituto de Investigaciones y Desarrollo Anzoategyi, Escuela de Medicina, Núcleo Anzoategui, Puerto La Cruz, Venezuela. eliadesl@latinmail.com
Eliades
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Ledezma
Alicia
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Jorquera
Herminia
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Bendezú
Julio
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Vivas
Gladinex
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Pérez
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D002454:Cell Differentiation; D004220:Disulfides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006131:Growth Inhibitors / Q000494:pharmacology*; D007891:Leishmania / Q000145:classification / Q000187:drug effects* / Q000648:ultrastructure*; D007896:Leishmaniasis / Q000517:prevention & control; D008018:Life Cycle Stages / Q000187:drug effects; D010936:Plant Extracts / Q000494:pharmacology*; D013454:Sulfoxides
D000981:Antiprotozoal Agents; D004220:Disulfides; D006131:Growth Inhibitors; D010936:Plant Extracts; D013454:Sulfoxides; C048980:ajoene