IQUIMEFA   05518
INSTITUTO QUIMICA Y METABOLISMO DEL FARMACO
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Effect of the sesquiterpene lactone deoxymikanolide on Trypanosoma cruzi infected mice and evaluation of its immunomodulatory activity on macrophage cells
Autor/es:
SANCHEZ ALBERTI, ANDRÉS; BORGO, JIMENA; CATALAN, CESAR A.; SULSEN, VALERIA; BIVONA, AUGUSTO E.; BEER, MARÍA F; ALONSO, MARÍA; LAURELLA, LAURA; CERNY, NATACHA; MALCHIODI, EMILIO L.; CAZORLA, SILVIA I.
Lugar:
CABA
Reunión:
Congreso; XI Congreso Argentino de Protozoología y Enfermedades Parasitarias. 1era Reunión Conjunta de Sociedades de Biociencias; 2017
Institución organizadora:
Sociedades de Biociencias
Resumen:
Chagas´ disease is a parasitic disease caused by the protozoan parasite Trypanosoma cruzi. It is considered, among others, a Neglected Tropical Disease. The drugs currently in use for the treatment of this parasitosis are not at all effective and have severe drawbacks. Nature has proved to be a rich source of bioactive compounds. Sequiterpenes lactones, present mainly in Asteraceae species, are interesting compounds due their pharmacological properties. Deoxymikanolide, isolated from Mikania spp., was active and selective against Trypanosoma cruzi epimastigotes, trypomastigotes and amastigotes (IC50% of 0.08, 1.5 and 6.3 µg/ml, respectively). Since deoxymikanolide presented significant in vitro activity and good selectivity on the different T. cruzi stages, the aim of this study was to evaluate its effect in an in vivo model of T. cruzi infection and its 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 body weight/day) for five consecutive days by the intraperitoneal route. Cytokine production was evaluated using RAW 264.7 macrophage cell line.Infected mice that received deoxymikanolide presented a lower blood 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 deoxymikanolide treated mice survived the acute phase of infection, 100% mortality was observed in control mice by day 22 post-infection. In vitro macrophage stimulation with 25 µg/mL deoxymikanolide produced a significant increase in the secretion of TNF-α and IL-12. This finding makes it an interesting lead molecule which may be useful for the development of new drugs for the treatment of Chagas disease.