The in vitro and in vivo effects of natural compounds on infective forms of trypanosoma cruzi

LOZANO E; SARTOR T; TONN C; NIETO M; GARCIA EE; SOSA MA

Congreso; 4th Annual World Congress of Microbs (WCM-2014); 2014

INTRODUCTION: Trypanosoma cruzi is a monoflagellate parasite that causes Chagas` disease. When T. cruzi is grown in liquid medium is mostly found as a non infective (proliferative) stage, and with a low percentage of the infective tripomastigote. Natural and synthetic compounds have been used against the parasite, although their use is restricted because the side cytotoxic effects on the hosts. Sesquiterpene lactones (STLs) and the diterpene 5-epi-icetexone (ICTX), (fig. 1) exhibited antiproliferative effect on epimastigote in cultures, and at certain concentrations showed cytostatic effects on infective and non infective forms. In addition, the compounds do not affect mammalian cell. AIMS: We proposed to evaluate the in vitro and in vivo effects of ICTX and sesquiterpene lactones on infective forms of T. cruzi . RESULTADOS: We observed that all the compounds inhibited the number of intracellular parasites (amastigotes (fig. 2 and 3) at low concentrations (1.5 a 3.8 μM non toxic for host cells). This effect was mostly observed after 48 h of incubation with the compounds. The percentage of replication was estimated (%R=RPx100/RPC), and we observed that the compounds decreased such percentages (fig 4). The treatments also reduced significantly the number of trypomastigotes rescued from the medium (fig 5), suggesting an effect either on the release or viability of the extracellular parasites. The STL helenalin showed to be the most deleterious. In infected mice we observed an increase of survival rate (from 50 to 80 %) after treatment with either BZN or ICTX (fig 6). In addition, the parasitemia decreased in mice treated with ICTX (0.3 mg/animal/day) (fig. 7) if compare with controls or treated with the vehicle DMSO. The effect of ICTX was at lesser extent than BZN (fig. 7). From the histological studies we observed the presence of parasite nests between muscle fibers in the heart of controls or treated with DMSO. In addition, a disorganization of the tissue and the presence of lymphocytes and macrophages, as well as necrosis in heart was observed in the infected animals. Treatment with ICTX or BZN canceled those effects (fig. 8). Finally, we observed a deleterious effect of ICTX on parasites recovered from the blood, being that effect stronger than BZN (fig. 9). CONCLUSIONS: We concluded that STLs and ICTX are effective against intracellular stages of T. cruzi, by inhibiting proliferation of amastigotes, although an additional effect on differentiation should not be discarded. The preliminar results on infected mice indicate that ICTX is as effective as BZN in reducing parasitemia that mimics the acute step of the disease. These findings indicate that terpenoid compounds could be excellent agents in the future for the fight against Chagas? disease.