Tratamiento antiparasitario de la infección por Trypansoma cruzi, durante la fase aguda experimental, combinando Benznidazol y Clomipramina.

STRAUSS MARIANA; LO PRESTI SILVINA; BAZÁN CAROLINA; BÁEZ ALEJANDRA; RIVAROLA WALTER; PAGLINI PATRICIA

Congreso; IX Congreso Argentino de Protozoología y Enfermedades Parasitarias.; 2011

Chagas disease is caused by the protozoan Trypanosoma cruzi and is widely distributed in Latin American countries. In Argentina, the only drug available for Chagas disease is benznidazole. This drug was synthesized in the 60´s, and it is only effective in the acute stage of the disease; besides it can have serious side-effects and there are also resistant strains to this drug. The pharmaceutical industry has restricted investment in research and development of new drugs for this disease. Tricyclic drugs: phenothiazines and tricyclic antidepressants such as clomipramine, inhibit trypanothione reductase T. cruzi exclusive enzyme, indispensable for the peroxides detoxification. This enzyme inhibition produces the T. cruzi death. Because of this effect in previous works of our lab we have demonstrated that clomipramine can be included as a potential chemotherapeutic agents. In this study we evaluated the simultaneous effect of Benznidazol (50mg/kg/día [Bz/2] y 100mg/kg/día [Bz]) + Clomipramina [Clo] (5mg/kg/dia) upon T. cruzi infection in the acute stage, in albino Swiss mice infected with 50/ mice tripomastigotes of T. cruzi Tulahuen strain. We used different doses of Bz and combinations with Clo. All treatments (Bz, Bz / 2, Clo Clo + Bz, Bz/2 + Clo) that were performed in this study produced decrease of parasite load, fewer inflammatory infiltrates and fibrosis in cardiac muscle, a decrease of electrocardiographic alterations and increased survival. The combinations of Bz + Clo caused a synergistic effect and demonstrated to be the most effective treatment showing that a lower dose of benznidazole and its combination with clomipramine is a good option to be considered as a drug for the treatment of Chagas disease in the acute stage.