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.
Ledezma
Eliades
E
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
Jorquera
Alicia
A
Bendezú
Herminia
H
Vivas
Julio
J
Pérez
Gladinex
G
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