Trypanothione reductase inhibitors: overview of the action of Thioridazine in different stages of Chagas disease.

LO PRESTI MS; BAZAN C; STRAUSS M; BAEZ AL; RIVAROLA HW; PAGLINI PA

ACTA TROPICA

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2015 p. 79 - 87

0001-706X

tThioridazine (TDZ) is a phenothiazine that has been shown to be one of the most potent phenothiazinesto inhibit trypanothione reductase irreversibly. Trypanothione reductase is an essential enzyme for thesurvival of Trypanosoma cruzi in the host. Here, we reviewed the use of this drug for the treatment of T.cruzi experimental infection. In our laboratory, we have studied the effect of TDZ for the treatment ofmice infected with different strains of T. cruzi and treated in the acute or in the chronic phases of theexperimental infection, using two different schedules: TDZ at a dose of 80 mg/kg/day, for 3 days starting1 h after infection (acute phase), or TDZ 80 mg/kg/day for 12 days starting 180 days post infection (d.p.i.)(chronic phase). In our experience, the treatment of infected mice, in the acute or in the chronic phases ofthe infection, with TDZ led to a large reduction in the mortality rates and in the cardiac histological andelectrocardiographical abnormalities, and modified the natural evolution of the experimental infection.These analyses reinforce the importance of treatment in the chronic phase to decrease, retard or stopthe evolution to chagasic myocardiopathy. Other evidence leading to the use of this drug as a potentialchemotherapeutic agent for Chagas disease treatment is also revised.