Mem Inst Oswaldo Cruz, Rio de Janeiro, VOLUME 117 | 2022
Perspective

Antioxidant defence system as a rational target for Chagas disease and Leishmaniasis chemotherapy

Ana Maria Murta Santi, Silvane Maria Fonseca Murta+

Fundação Oswaldo Cruz-Fiocruz, Instituto René Rachou, Grupo de Genômica Funcional de Parasitos, Belo Horizonte, MG, Brasil

DOI: 10.1590/0074-02760210401
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ABSTRACT

Chagas disease and leishmaniasis are neglected tropical diseases caused by the protozoan parasites Trypanosoma cruzi and Leishmania spp., respectively. They are among the most important parasitic diseases, affecting millions of people worldwide, being a considerable global challenge. However, there is no human vaccine available against T. cruzi and Leishmania infections, and their control is based mainly on chemotherapy. Treatments for Chagas disease and leishmaniasis have multiple limitations, mainly due to the high toxicity of the available drugs, long-term treatment protocols, and the occurrence of drug-resistant parasite strains. In the case of Chagas disease, there is still the problem of low cure rates in the chronic stage of the disease. Therefore, new therapeutic agents and novel targets for drug development are urgently needed. Antioxidant defence in Trypanosomatidae is a potential target for chemotherapy because the organisms present a unique mechanism for trypanothione-dependent detoxification of peroxides, which differs from that found in vertebrates. Cellular thiol redox homeostasis is maintained by the biosynthesis and reduction of trypanothione, involving different enzymes that act in concert. This study provides an overview of the antioxidant defence focusing on iron superoxide dismutase A, tryparedoxin peroxidase, and ascorbate peroxidase and how the enzymes play an important role in the defence against oxidative stress and their involvement in drug resistance mechanisms in T. cruzi and Leishmania spp.

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Financial support: CNPq (304158/2019-4), FIOCRUZ (Convênio Fiocruz-Institut Pasteur-USP and Programa INOVA FIOCRUZ), FAPEMIG (APQ-02816-21).
SMFM is research fellow supported by CNPq and AMMS is supported by CAPES.
+ Corresponding author: silvane.murta@fiocruz.br
ORCID http://orcid.org/0000-0002-8523-2155
Received 20 December 2021
Accepted 27 December 2021

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