5-o-metylembelin induces antiproliferative effect on Trypanosoma cruzi

SPINA R; AGÜERO M; BARRERA P; SOSA, M; FERESIN, G; LOZANO, E; TAPIA A

Merlo , San Luis

Congreso; XXXV Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2017

Sociedad de Biologia de Cuyo

Chagas? disease is a zoonotic pathology, caused by Trypanosoma cruzi. In San Juan Province, decoctions of Oxalis erythrorhiza Gillies ex Hooker et Arnott (Oxalidaceae), are recommended for hepatic and heart complains. Its main compound embelin was active against T. cruzi, a possible link between the traditional use and the trypanocidal effect was suggested. Additionally, activity against protozoan of its methylated derivative 5O-methylembelin (ME) was assayed. ME showed that is more active against T. cruzi epimastigotes than embelin. To elucidate the mechanism of action of ME, its effect by transmission electron microscopy was evaluated. Results indicate a mitochondrial swelling, in line with alterations in mitochondrial activity, observed by MTT assay. Additionally, an increase in ROS generation was detected with H2DCFDA probe. In order to evaluate the influence of ROS in epimastigote proliferation, parasites were incubated in Diamond medium for 3 days in presence of ME or with ME and GSH. The addition of GSH reversed partially the antiproliferative effects. To extend this information to other parasite stages, Vero cells were infected with T. cruzi (48 h) and subsequently, the medium was removed and cells were treated with 16µM ME (24h). Afterwards, the cells were fixed and stained with Giemsa to evaluate the infection percentage and intracellular amastigotes. The number of treated cells containing more than 20 amastigotes, compared to untreated cells present significant differences. In conclusion the ability of ME to reduce the parasite load becomes it in a special candidate for the treatment of chronic Chagas disease.