Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

The Therapeutic Potential of Angeli’s Salt in Mitigating Acute Trypanosoma Cruzi Infection in Mice

Vera Lúcia Hideko Tatakihara
,
Aparecida Donizette Malvezi
,
Rito Santo Pereira
ORCID logo ,
Bruno Fernando Cruz Lucchetti
ORCID logo ,
Lucas Felipe Dos Santos
,
Rubens Cecchini
,
Lucy Megumi Yamauchi
ORCID logo ,
Sueli Fumie Yamada-Ogatta
ORCID logo ,
Katrina M Miranda
,
Waldiceu Aparecido Verri Jr
ORCID logo ,
Marli Cardoso Martins-Pinge
,
Phileno Pinge-Filho
* ORCID logo
Version 1 : Received: 21 June 2023 / Approved: 22 June 2023 / Online: 22 June 2023 (12:17:36 CEST)

A peer-reviewed article of this Preprint also exists.

Hideko Tatakihara, V.L.; Malvezi, A.D.; Pereira, R.S.; Lucchetti, B.F.C.; Dos Santos, L.F.; Cecchini, R.; Yamauchi, L.M.; Yamada-Ogatta, S.F.; Miranda, K.M.; Verri, W.A.; Martins-Pinge, M.C.; Pinge-Filho, P. The Therapeutic Potential of Angeli’s Salt in Mitigating Acute Trypanosoma cruzi Infection in Mice. Pathogens 2023, 12, 1063. Hideko Tatakihara, V.L.; Malvezi, A.D.; Pereira, R.S.; Lucchetti, B.F.C.; Dos Santos, L.F.; Cecchini, R.; Yamauchi, L.M.; Yamada-Ogatta, S.F.; Miranda, K.M.; Verri, W.A.; Martins-Pinge, M.C.; Pinge-Filho, P. The Therapeutic Potential of Angeli’s Salt in Mitigating Acute Trypanosoma cruzi Infection in Mice. Pathogens 2023, 12, 1063.

Abstract

Chagas disease (CD), caused by Trypanosoma cruzi, is a neglected tropical disease prevalent in Latin America. The treatment of infected patients is aimed at eliminating the parasite, reducing the risk of cardiomyopathy, and interrupting the disease transmission cycle. At present, the World Health Organization only recognizes benznidazole (BZ) and nifurtimox as effective drugs for treating CD. However, 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, critical for controlling parasite proliferation and CD evolution. Compounds that liberate nitric oxide (NO) (NO donors) have been used as therapeutic agents against T. cruzi. However, to date, there is no evidence about the related nitrogen oxide, nitroxyl (HNO) on the outcome of T. cruzi infection. In this study, we investigated the effect of the HNO donor Angeli's salt (AS) on C57BL/6 mice infected with T. cruzi (Y strain, 5 × 103 trypomastigotes, i.p.). The use of AS showed positive results, such as a decrease in the number of parasites present in the bloodstream and in nests within the heart, as well as improved the protective antioxidant capacity of erythrocytes in infected animals, leading to an overall decrease in the severity of the disease. Furthermore, in vitro experiments showed that AS treatment reduced parasite uptake and the release of trypomastigotes by macrophages. Taken together, these findings from both the mouse model and in vitro testing suggest that AS could be a promising therapy for CD.

Keywords

Chagas disease; Therapy; Nitroxyl; Leukopenia; Thrombocytopenia; Oxidative stress; Macrophages

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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