Actions of Angeli's salt, a nitroxyl (HNO) donor, on Trypanosoma cruzi infection

Abstract

Chagas disease, caused by Trypanosoma cruzi infection, is endemic to much of Latin America, but also present in the United States (U.S.) The goal of treatment is to eliminate the parasite and decrease the probability of cardiomyopathy and interrupt the cycle of disease transmission. Currently, only benznidazole (BZN) and nifurtimox are recognized by the World Health Organization as effective drugs for treatment of Chagas disease, but both present low cure rates in the chronic phase and often have serious side effects. T. cruzi infection produces an intense inflammatory response in several tissues which is critical for controlling parasites proliferation and evolution of Chagas disease. Compounds liberating nitric oxide (NO donors) have been used as therapeutic agents against T. cruzi. Here we test HNO donor, Angeli's salt (AS) in the outcome of T. cruzi infection. C57BL/6 mice were infected with T. cruzi (Y strain, 5 × 103 trypomastigotes) intraperitoneally (ip). After 15 minutes of infection and the subsequent 12 days, the animals were treated with different concentrations of AS ip. The control group received 100 uL of PBS by the same route. Treatment with AS showed decreased parasitemia and in the number of nests in the cardiac tissue, decreased oxidative stress in erythrocytes and improved leukopenia and thrombocytopenia resulting in reduced disease severity. The in vitro treatment was able to reduce the parasite internalization rate and release of infective trypomastigotes by these cells. Our results suggest for the first time the therapeutic potential of AS in a mouse model of Chagas disease.Support or Funding InformationCAPES, Fundação Araucária, CNPQ, UniZambeze and MCTESTP Mozambique.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.