Lactones affect invasiveness of L.mexicana possibly by reducing expression of virulence factors

BARRERA P; JIMENEZ-ORTIZ V; CARVELLI L; SARTOR T; SANCHEZ V; TONN C; GIORDANO O; SOSA MA

Mar del Plata (Buenos Aires)

Congreso; XLIII Reunión Anual de SAIB.; 2007

SAIB

Leishmania mexicana is the etiological agent of the cutaneous leishmaniasis. For decades, many natural compounds have been used against leishmaniasis, but its use has been restricted due the high citotoxicity on host cells. Leishmania synthesizes high-mannose containing glycoconjugates as virulence factors to invade the host cells. Gp63 is a virulence factor, which is synthesized by the action of GDP-mannose pyrophosphorylase (GDP-MP). In this study we proposed to evaluate the effect of three sesquiterpene lactones (SL); helenalin (Hln), mexicanin (Mxc) and dehydroleucodin (DhL) on the life clycle of L. mexicana, and the ability to invade host cells. Methods: The effect of SL was evaluated on cultured promastigotes of L. mexicana. The infective index was determinated by counting number of infected host cells and number of parasites per cell, after stainning with hematoxylin-eosin. Expression of virulence factors was evaluated by western blot. Apoptosis was observed by TUNEL methods. Results and conclusions: The three compounds diminished proliferation of parasites, possibly by inducing apoptosis. They also reduced invasive ability to Vero cells and the expression of GDP-MP and gp63 was decreased significantly by Hln and at lesser extent by Mxc and DhL.