EFFECT OF THE SESQUITERPENE LACTONE DEOXYMIKANOLIDE ON TRYPANOSOMA CRUZI INFECTED MICE AND EVALUATION OF ITS IMMUNOMODULATORY ACTIVITY ON MACROPHAGE CELLS

LAURELLA, LAURA; SANCHEZ ALBERTI, ANDRÉS; BIVONA, AUGUSTO E.; CERNY, NATACHA; BORGO, JIMENA; BEER, MARÍA F; MALCHIODI, EMILIO L.; CATALAN, CESAR A.; ALONSO, MARÍA; CAZORLA, SILVIA I.; SULSEN, VALERIA

CABA

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS 2017; 2017

Chagas? disease is a parasitic disease caused by the protozoanparasite Trypanosoma cruzi. It is considered, among others,a Neglected Tropical Disease. The drugs currently in use for thetreatment of this parasitosis are not at all effective and have severedrawbacks. Nature has proved to be a rich source of bioactivecompounds. Sequiterpenes lactones, present mainly in Asteraceaespecies, are interesting compounds due their pharmacological properties.Deoxymikanolide, isolated from Mikania spp., was active and selectiveagainst Trypanosoma cruzi epimastigotes, trypomastigotesand amastigotes (IC50% of 0.08, 1.5 and 6.3 μg/ml, respectively).Since deoxymikanolide presented significant in vitro activity andgood selectivity on the different T. cruzi stages, the aim of this studywas to evaluate its effect in an in vivo model of T. cruzi infection andits immunomodulatory activity on macrophage cells.Balb/c mice were infected with a lethal dose of T. cruzi (RA strain)and treated with deoxymikanolide or benznidazole (1 mg/kg of bodyweight/day) for five consecutive days by the intraperitoneal route.Cytokine production was evaluated using RAW 264.7 macrophagecell line.Infected mice that received deoxymikanolide presented a lowerblood parasitemia, as compared to control. In deoxymikanolide-treated mice, a significant decrease in the mortality caused by T.cruzi infection was observed. While nearly 70% of deoxymikanolidetreated mice survived the acute phase of infection, 100% mortalitywas observed in control mice by day 22 post-infection.In vitro macrophage stimulation with 25 μg/mL deoxymikanolideproduced a significant increase in the secretion of TNF-α and IL-12.This finding makes it an interesting lead molecule which may beuseful for the development of new drugs for the treatment of Chagasdisease.