Ursolic acid promotes clearance of Trypanosoma cruzi amastigotes in the host cell

MARTINEZ, SANTIAGO JOSE; ROMANO, PATRICIA SILVIA; MUÑOZ, LUCILA IBEL; VANRELL, MARÍA CRISTINA; SALASSA, BETIANA NEBAÍ

Virtual

Congreso; IECBM 2020; 2020

Trypanosoma cruzi is the etiological agent of Chagas disease, which is endemic in LatinAmerica. Ursolic acid (UA) is a natural pentacyclic triterpene which has been shown to reduce thepeak of parasitemia in T. cruzi infected mice. Due to UA was described as an inducer of autophagyand having into account that our previous work established the protective role of this process on invivo infections, we decided to study the possible involvement of UA in the elimination of parasitesin macrophages and cardiac cells and its possible mechanism of action.To test this, we infected cellswith T. cruzi for 24 hours, and then treated the samples with UA (5-10 μM) for different times. Ourdata showed that UA significantly decreased the amount of amastigotes compared to non-treatedcells. We also studied the effect of UA on the autophagy response and other possible mechanismsof action we observed that UA induces the autophagy pathway, and that LC3, the marker ofautophagy, is recruited around amastigotes, indicating xenophagy of these parasites. A cytotoxiceffect was observed on T. cruzi trypomastigotes while epimastigotes displayed more resistance tothis drug. Moreover, the production of ROS after 24 hours of treatment is increased on infected cellsbut, interestingly, UA does not have this effect on non-infected cells. We conclude that this naturalcompound promotes parasite death through induction of autophagy and other host cell responses.