TY - JOUR
T1 - The Therapeutic Potential of Angeli’s Salt in Mitigating Acute Trypanosoma cruzi Infection in Mice
AU - Hideko Tatakihara, Vera Lúcia
AU - Malvezi, Aparecida Donizette
AU - Pereira, Rito Santo
AU - Lucchetti, Bruno Fernando Cruz
AU - Dos Santos, Lucas Felipe
AU - Cecchini, Rubens
AU - Yamauchi, Lucy Megumi
AU - Yamada-Ogatta, Sueli Fumie
AU - Miranda, Katrina M.
AU - Verri, Waldiceu A.
AU - Martins-Pinge, Marli Cardoso
AU - Pinge-Filho, Phileno
N1 - Publisher Copyright: © 2023 by the authors.
PY - 2023/8
Y1 - 2023/8
N2 - Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical disease prevalent in Latin America. Infected patients are treated to eliminate the parasite, reduce the cardiomyopathy risk, and interrupt the disease transmission cycle. The World Health Organization recognizes benznidazole (BZ) and nifurtimox as effective drugs for CD treatment. In the chronic phase, both drugs have low cure rates and serious side effects. T. cruzi infection causes intense tissue inflammation that controls parasite proliferation and CD evolution. Compounds that liberate nitric oxide (NO) (NO donors) have been used as anti-T. cruzi therapeutics. Currently, there is no evidence that nitroxyl (HNO) affects T. cruzi infection outcomes. This study investigated the effects of the HNO donor Angeli’s salt (AS) on C57BL/6 mice infected with T. cruzi (Y strain, 5 × 103 trypomastigotes, intraperitoneally). AS reduced the number of parasites in the bloodstream and heart nests and increased the protective antioxidant capacity of erythrocytes in infected animals, reducing disease severity. Furthermore, in vitro experiments showed that AS treatment reduced parasite uptake and trypomastigote release by macrophages. Taken together, these findings from the murine model and in vitro testing suggest that AS could be a promising therapy for CD.
AB - Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical disease prevalent in Latin America. Infected patients are treated to eliminate the parasite, reduce the cardiomyopathy risk, and interrupt the disease transmission cycle. The World Health Organization recognizes benznidazole (BZ) and nifurtimox as effective drugs for CD treatment. In the chronic phase, both drugs have low cure rates and serious side effects. T. cruzi infection causes intense tissue inflammation that controls parasite proliferation and CD evolution. Compounds that liberate nitric oxide (NO) (NO donors) have been used as anti-T. cruzi therapeutics. Currently, there is no evidence that nitroxyl (HNO) affects T. cruzi infection outcomes. This study investigated the effects of the HNO donor Angeli’s salt (AS) on C57BL/6 mice infected with T. cruzi (Y strain, 5 × 103 trypomastigotes, intraperitoneally). AS reduced the number of parasites in the bloodstream and heart nests and increased the protective antioxidant capacity of erythrocytes in infected animals, reducing disease severity. Furthermore, in vitro experiments showed that AS treatment reduced parasite uptake and trypomastigote release by macrophages. Taken together, these findings from the murine model and in vitro testing suggest that AS could be a promising therapy for CD.
KW - Chagas disease
KW - leukopenia
KW - macrophages
KW - nitroxyl
KW - oxidative stress
KW - therapy
KW - thrombocytopenia
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U2 - 10.3390/pathogens12081063
DO - 10.3390/pathogens12081063
M3 - Article
SN - 2076-0817
VL - 12
JO - Pathogens
JF - Pathogens
IS - 8
M1 - 1063
ER -