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.
Highlights
Chagas disease and leishmaniasis are infectious, parasitic diseases caused by protozoan parasites of the Trypanosomatidae family
Antioxidant defence - Trypanosomatids are frequently exposed to different reactive oxygen species (ROS), such as superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals, produced by cellular metabolism and external agents, including products of the immune response of the host and drug metabolism.[7]. Since ROS can damage various cellular components, including membrane lipids, nucleic acids, and proteins, all organisms possess defence mechanisms based on antioxidant enzymes.[8] trypanosomatid cells lack catalase, selenium-dependent glutathione peroxidase (GPX), glutathione reductase, and thioredoxin reductase.[7,9] Instead, Trypanosomatids possess a peculiar antioxidant defence mechanism based on the low molecular mass dithiol trypanothione [bis(glutathionyl)spermidine; T(SH)2].(7,10,11,12) The trypanothione is a central thiol that online | memorias.ioc.fiocruz.br
Iron superoxide dismutase A - FeSOD-A is an important enzyme in the antioxidant defence system that protects parasites against superoxide radicals (O2−), which are converted to oxygen (O2) and hydrogen peroxide (H2O2).(12) H2O2 is metabolised by different enzymes with peroxidase activity, such as tryparedoxin peroxidase (TXN), ascorbate peroxidase (APX), peroxiredoxins (PRXs), and glutathione peroxidases (GPXs).(14)
Summary
Chagas disease and leishmaniasis are infectious, parasitic diseases caused by protozoan parasites of the Trypanosomatidae family. We describe studies of FeSODs, TXNPx, and APX, in relation to the important roles they play in defending oxidative stress and their involvement in drug resistance mechanisms in T. cruzi and Leishmania spp.
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