Trypanothione reductase inhibitors: Overview of the action of thioridazine in different stages of Chagas disease

Acta Tropica
M S Lo PrestiPatricia Paglini-Oliva

Abstract

Thioridazine (TDZ) is a phenothiazine that has been shown to be one of the most potent phenothiazines to inhibit trypanothione reductase irreversibly. Trypanothione reductase is an essential enzyme for the survival 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 of mice infected with different strains of T. cruzi and treated in the acute or in the chronic phases of the experimental infection, using two different schedules: TDZ at a dose of 80 mg/kg/day, for 3 days starting 1h 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 of the infection, with TDZ led to a large reduction in the mortality rates and in the cardiac histological and electrocardiographical 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 stop the evolution to chagasic myocardiopathy. Other evidence leading to the use of this drug...Continue Reading

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Citations

Jan 10, 2016·Acta Tropica·José BermudezSantiago Palma
Nov 26, 2015·Molecular and Biochemical Parasitology·Alejandro E Leroux, R Luise Krauth-Siegel
Nov 9, 2017·Revista Do Instituto De Medicina Tropical De São Paulo·Michelly Cristina MontenoteLuciamáre Perinetti Alves Martins
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Dec 9, 2021·Future Microbiology·Dandugudumula Ramu, Shailja Singh

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