Structural, ultrastructural studies and evolution of Trypanosoma cruzi-infected mice treated with thioridazine.

ABSTRACT

Thioridazine (THI) is a tricyclic drug that belongs to the phenothiazine series. THI had a lethal effect upon epimastigotes in culture medium in a concentration of 0.5 microM. Trypanocidal effect upon trypomastigotes of Trypanosoma cruzi was observed above 0.5 mM of THI. Ultrastructural studies showed intracellular vacuoles in both parasite forms and mitochondrion reorganization. To analyze the use of THI as a therapy, male mice were inoculated with 7.10(4) trypomastigotes of T. cruzi, Tulahuen strain, and treated with THI for 3 days, with 80 mg/kg/day. Survival and parasitemia of mice treated with lower doses were similar to those observed in the control group (14 days postinfection). THI treatment modified parasitemia levels. They were negative by day 20 p.i. Hearts from control untreated mice presented typical chagasic myocarditis. Hearts from THI-treated mice sacrificed by day 30 p.i. showed inflammatory infiltrates without amastigote nests. Three months postinfection a mild infiltrate located in the interventricular septum was observed. Survival of this group was 9 months. Present results show that THI had a direct effect upon parasitemia, improved survival of treated mice, and modified the evolution of experimental Chagas disease.