Activity against Trypanosoma cruzi (Tulahuen) and ultrastructural alterations induced by psilostachyin

BARRERA P; SULSEN, VALERIA; MUSCHIETTI L; MARTINO V; SOSA MA

Cuiabá

Simposio; IV SIMPOSIO IBEROAMERICANO DE PLANTAS MEDICINAIS.; 2009

Sociedad Argentina de Protozoología

Chagas´disease or American trypanosomiasis is a major health problem in Latin America. The side effects and the emerging resistance to available drugs have led to the urgent need for new therapeutic agents against this disease. As a result of our ongoing search of antiparasitic compounds, from natural sources, we have recently reported the in vitro and in vivo activity of psilostachyin, a sesquiterpene lactone (STL) isolated from Ambrosia tenuifolia, against Trypanosoma cruzi RA strain (1). Herein, we describe the effects of this compound on the growth, viability and morphology of cultured epimastigotes of T. cruzi (Tulahuen strain). The in vitro trypanocidal activity was evaluated by counting the parasites in a Neubauer Chamber, and the viability, by using the technique of dye exclusion (2). Moreover, we have studied the effects of psilostachyin on the ultrastructure of the parasites by transmission electron microscopy (TEM). The compound is highly active against T. cruzi (Tulahuen), since at concentrations as low as 0.5 µg/ml it inhibited the growth of parasites, even for short periods of incubation. However, the estimated IC50 for this compound was between 1.8 and 2.0 µg/ml, indicating that at concentrations of 0.5-1.0 µg/ml it could act primarily as a cytostatic agent. The effect of psilostachyn on growth of parasites was partially reversible at low concentrations (< 1.5 μg/ml) or irreversible at concentrations higher than 2 ug / ml. It has been suggested that the cytotoxicity of many STLs is mediated by interaction with sulphydryl groups of proteins involved in cell metabolism. However, this is not the case for psilostachyin since neither dithiotreitol nor glutathione could reverse the effect of the compound. Interestingly, the compound induced ultrastructural alterations on the parasites, since from 1 µg/ml it was observed an important mitochondrial swelling, and deformity in kinetoplast, consistent with an altered metabolism (3). According to the results obtained, psilostachyin can be considered a promising candidate for the development of a new therapeutic agent for the treatment of Chagas disease.