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

SÜLSEN V; BARRERA P; MUSCHIETTI L; MARTINO V; SOSA M

Cuiaba, Mato Grosso, Brasil

Simposio; IV Simpósio Iberoamericano de Plantas Medicinais; 2009

Programa Iberoamericano De Ciencia Y Tecnologia Para El Desarrollo (CYTED)

Introduction: Chagas´disease or American Trypanosomiasis is a major health problem in Latin America and new therapeutic agents are urgently needed. As a result of our ongoing search of antiparasitic compounds, from natural sources, we have recently reported the activity of psilostachyin, a sesquiterpene lactone isolated from Ambrosia tenuifolia, against Trypanosoma cruzi RA strain (1). Objective: The aim of this study was to evaluate the effects of psilostachyin on the growth, viability and morphology of cultured epimastigotes of T. cruzi (Tulahuen strain).   Material and Methods: 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). The effects of psilostachyin on the ultrastructure of the parasites were determined by transmission electron microscopy. Results and discussion: Psilostachyin is highly active against T. cruzi (Tulahuen), since at concentrations as low as 0.5 µg/ml it inhibited the growth of parasites. The effect was irreversible and 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, an important mitochondrial swelling and deformity in kinetoplast was observed, consistent with an altered metabolism (3). Conclusion: Psilostachyin exerted significant in vitro trypanocidal activity against T. cruzi epimastigotes (Tulahuen) and induced ultrastructure alterations in the parasite. 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. Grant: This investigation was supported in part by PIP-CONICET (2009-2011) and UBACYT B030 (UBA). References 1. Sülsen V. et al. 2008. Antimicrob.AgentsChemother. 52(7):2415-2419. 2. Jimenez-Ortiz V. et al. 2005. J Parasitol. 9(1):170-174. 3. Rodrigues J.C. et al. 2005. Exp Parasitol. 111(4):230-238.