The Therapeutic Potential of Angeli’s Salt in Mitigating Acute <i>Trypanosoma cruzi</i> Infection in Mice
Chagas disease (CD), caused by <i>Trypanosoma cruzi</i>, 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 recogn...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/12/8/1063 |
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| author | Vera Lúcia Hideko Tatakihara Aparecida Donizette Malvezi Rito Santo Pereira Bruno Fernando Cruz Lucchetti Lucas Felipe Dos Santos Rubens Cecchini Lucy Megumi Yamauchi Sueli Fumie Yamada-Ogatta Katrina M. Miranda Waldiceu A. Verri Marli Cardoso Martins-Pinge Phileno Pinge-Filho |
| author_facet | Vera Lúcia Hideko Tatakihara Aparecida Donizette Malvezi Rito Santo Pereira Bruno Fernando Cruz Lucchetti Lucas Felipe Dos Santos Rubens Cecchini Lucy Megumi Yamauchi Sueli Fumie Yamada-Ogatta Katrina M. Miranda Waldiceu A. Verri Marli Cardoso Martins-Pinge Phileno Pinge-Filho |
| author_sort | Vera Lúcia Hideko Tatakihara |
| collection | DOAJ |
| description | Chagas disease (CD), caused by <i>Trypanosoma cruzi</i>, 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. <i>T. cruzi</i> 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-<i>T. cruzi</i> therapeutics. Currently, there is no evidence that nitroxyl (HNO) affects <i>T. cruzi</i> infection outcomes. This study investigated the effects of the HNO donor Angeli’s salt (AS) on C57BL/6 mice infected with <i>T. cruzi</i> (Y strain, 5 × 10<sup>3</sup> 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. |
| first_indexed | 2024-03-10T23:39:34Z |
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| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T23:39:34Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-6f4676c9be2945059b5b9683424621b82023-11-19T02:33:05ZengMDPI AGPathogens2076-08172023-08-01128106310.3390/pathogens12081063The Therapeutic Potential of Angeli’s Salt in Mitigating Acute <i>Trypanosoma cruzi</i> Infection in MiceVera Lúcia Hideko Tatakihara0Aparecida Donizette Malvezi1Rito Santo Pereira2Bruno Fernando Cruz Lucchetti3Lucas Felipe Dos Santos4Rubens Cecchini5Lucy Megumi Yamauchi6Sueli Fumie Yamada-Ogatta7Katrina M. Miranda8Waldiceu A. Verri9Marli Cardoso Martins-Pinge10Phileno Pinge-Filho11Laboratório de Imunopatologia Experimental, Departamento de Imunologia, Parasitologia e Patologia Geral, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina 86057-970, Paraná, BrazilLaboratório de Imunopatologia Experimental, Departamento de Imunologia, Parasitologia e Patologia Geral, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina 86057-970, Paraná, BrazilLaboratório de Imunopatologia Experimental, Departamento de Imunologia, Parasitologia e Patologia Geral, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina 86057-970, Paraná, BrazilLaboratório de Fisiologia e Fisiopatologia Cardiovascular, Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina 86057-970, Paraná, BrazilLaboratório de Imunopatologia Experimental, Departamento de Imunologia, Parasitologia e Patologia Geral, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina 86057-970, Paraná, BrazilLaboratório de Fisiopatologia e Radicais Livres, Departamento de Imunologia, Parasitologia e Patologia Geral, Universidade Estadual de Londrina, Londrina 86057-970, Paraná, BrazilLaboratório de Biologia Molecular de Microrganismos, Departamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina 86057-970, Paraná, BrazilLaboratório de Biologia Molecular de Microrganismos, Departamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina 86057-970, Paraná, BrazilDepartment of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USALaboratório de Pesquisa em Dor, Inflamação, Neuropatia e Câncer, Departamento de Imunologia, Parasitologia e Patologia Geral, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina 86057-970, Paraná, BrazilDepartamento de Fisioterapia, Centro Universitário do Vale do Araguaia, Barra do Garças 78603-209, Mato Grosso, BrazilLaboratório de Imunopatologia Experimental, Departamento de Imunologia, Parasitologia e Patologia Geral, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina 86057-970, Paraná, BrazilChagas disease (CD), caused by <i>Trypanosoma cruzi</i>, 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. <i>T. cruzi</i> 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-<i>T. cruzi</i> therapeutics. Currently, there is no evidence that nitroxyl (HNO) affects <i>T. cruzi</i> infection outcomes. This study investigated the effects of the HNO donor Angeli’s salt (AS) on C57BL/6 mice infected with <i>T. cruzi</i> (Y strain, 5 × 10<sup>3</sup> 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.https://www.mdpi.com/2076-0817/12/8/1063Chagas diseasetherapynitroxylleukopeniathrombocytopeniaoxidative stress |
| spellingShingle | Vera Lúcia Hideko Tatakihara Aparecida Donizette Malvezi Rito Santo Pereira Bruno Fernando Cruz Lucchetti Lucas Felipe Dos Santos Rubens Cecchini Lucy Megumi Yamauchi Sueli Fumie Yamada-Ogatta Katrina M. Miranda Waldiceu A. Verri Marli Cardoso Martins-Pinge Phileno Pinge-Filho The Therapeutic Potential of Angeli’s Salt in Mitigating Acute <i>Trypanosoma cruzi</i> Infection in Mice Pathogens Chagas disease therapy nitroxyl leukopenia thrombocytopenia oxidative stress |
| title | The Therapeutic Potential of Angeli’s Salt in Mitigating Acute <i>Trypanosoma cruzi</i> Infection in Mice |
| title_full | The Therapeutic Potential of Angeli’s Salt in Mitigating Acute <i>Trypanosoma cruzi</i> Infection in Mice |
| title_fullStr | The Therapeutic Potential of Angeli’s Salt in Mitigating Acute <i>Trypanosoma cruzi</i> Infection in Mice |
| title_full_unstemmed | The Therapeutic Potential of Angeli’s Salt in Mitigating Acute <i>Trypanosoma cruzi</i> Infection in Mice |
| title_short | The Therapeutic Potential of Angeli’s Salt in Mitigating Acute <i>Trypanosoma cruzi</i> Infection in Mice |
| title_sort | therapeutic potential of angeli s salt in mitigating acute i trypanosoma cruzi i infection in mice |
| topic | Chagas disease therapy nitroxyl leukopenia thrombocytopenia oxidative stress |
| url | https://www.mdpi.com/2076-0817/12/8/1063 |
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