Chagas disease is a tropical illness caused by the protozoan Trypanosoma cruzi. The disease affects populations of the Americas and has been spread to other continents due to the migration process. The disease is partially controlled by two drugs, Benznidazole and Nifurtimox. These molecules are active in the acute phase of the infection but are usually ineffective during the symptomatic chronic phase. Several research groups have developed novel candidates to control Chagas disease; however, no novel commercial formulation is available. In this article, we described the anti-T. cruzi effects of phenothiazinium dyes in amastigote and trypomastigote forms of the parasite. Methylene Blue, New Methylene Blue, Toluidine Blue O, and 1,9-Dimethyl Methylene Blue inhibited the parasite proliferation at nanomolar concentrations and also demonstrated low toxicity in host cells. Moreover, combinations of phenothiazinium dyes indicated a synergic pattern against amastigotes compared to the Benznidazole counterparts. Phenothiazinium dyes levels of reactive oxygen species (ROS) and decreased the mitochondrial potential in trypomastigotes, indicating the mechanism of action of the dyes in T. cruzi. Our article offers a basis for future strategies for the control of Chagas disease using low-cost formulations, an important point for endemic underdeveloped regions.

Cardiac damage during the acute phase of Chagas disease (CD) is associated with an increase in pro-inflammatory markers and oxidative stress. Melatonin has emerged as a promising therapy for CD due to its antioxidant and immunomodulatory properties. However, the protective action of melatonin in the cardiac tissue as well as its direct action on the parasite cycle is not fully understood. We investigated the effects of melatonin on heart parasitism in mice infected with Trypanosoma cruzi (T. cruzi) and also its effects on the parasitic proliferation in vitro. Our in vivo study showed that melatonin reduced circulating parasitemia load, but did not control tissue (heart, liver and spleen) parasitism in mice. Melatonin did not prevent the redox imbalance in the left ventricle of infected mice. Our in vitro findings showed that melatonin did not inhibit parasites replication within cells, but rather increased their release from cells. Melatonin did not control parasitism load in the heart or prevented the cardiac redox imbalance induced by acute T. cruzi infection. The hormone controlled the circulating parasitic load, but in cells melatonin accelerated parasitic release, a response that can be harmful.

Sampaio Oliveira, P. A. Consequences of hypothyroidism in experimental Chagas disease. 2022. 100 f. Tese.

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