Zileuton, a 5-Lypoxigenase Inhibitor, is Antiparasitic and Prevents Inflammation in the Chronic Stage of Heart Chagas Disease
Chronic Chagas cardiomyopathy is associated with an unbalanced immune response and impaired heart function, and available drugs do not prevent its development. Zileuton (Zi), a 5-lypoxigenase inhibitor, affects inflammatory/pro-resolution mediators. Herein, Zi treatment in the early phase of infection reduced parasitemia associated mainly with the direct effect of Zi on the parasite, and the enzyme epoxide hydrolase was the potential molecular target behind the trypanocidal effect. In the intermediate acute phase of infection, Zi reduced the number of innate and adaptive inflammatory cells, increased the level of SOCS2 expression in the heart associated with lower inflammation, and improved cardiac function. Zi treatment initiated in the chronic stage increased the level of SOCS2 expression in the heart, reduced inflammation, and improved cardiac function. Our data suggest that Zi protects against <i>Trypanosoma cruzi</i> infection by acting directly on the parasite and reducing heart damage and is a promising option for the treatment of Chagas disease.
Authors
- Elany Barbosa da Silva (ORCID: https://orcid.org/0000-0002-1926-3500)
- Ronan Ricardo Sabino Araújo
- Felipe S. Chambergo (ORCID: https://orcid.org/0000-0001-7567-0656)
- Nazareth N. Rocha (ORCID: https://orcid.org/0000-0003-0921-8068)
- Rafaela das Dores Pereira (ORCID: https://orcid.org/0000-0002-1007-8480)
- Mauro Martins Teixeira (ORCID: https://orcid.org/0000-0002-6944-3008)
- Estela Mariana Guimarães Lourenço (ORCID: https://orcid.org/0000-0003-2708-4526)
- Danilo Roman‐Campos (ORCID: https://orcid.org/0000-0002-2690-912X)
- Rafaela Salgado Ferreira (ORCID: https://orcid.org/0000-0003-3324-0601)
- Jáder Santos Cruz (ORCID: https://orcid.org/0000-0003-1365-2318)
- Mayra Fernanda Ricci (ORCID: https://orcid.org/0000-0003-2074-1204)
- Gabriel Stephani de Oliveira (ORCID: https://orcid.org/0000-0002-9261-0310)
- Fabiana S. Machado (ORCID: https://orcid.org/0000-0001-9272-5209)
- Fernando Bento Rodrigues Oliveira
Institutions
- Universidade Federal de Minas Gerais (BR)
- Universidade Federal Fluminense (BR)
- Universidade de São Paulo (BR)
- Universidade Federal de São Paulo (BR)
Publication Details
- Journal
- ACS Infectious Diseases
- Published
- 2024-11-28
- DOI
- https://doi.org/10.1021/acsinfecdis.4c00623
- Citations
- 1
- Primary Topic
- Trypanosoma species research and implications
- Type
- article
- Field-Weighted Citation Impact
- 0.39
Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação de Amparo à Pesquisa do Estado de Minas Gerais
- Universidade Federal de Minas Gerais
- Universidade Federal Fluminense
- Directorate for Biological Sciences