| Author | Ribeiro, Juliana Martins | |
| Author | Teixeira, Eliane de Morais | |
| Author | Alves, Líndicy Leidicy | |
| Author | Alves, Érica Alessandra Rocha | |
| Author | Xavier, Marcelo Antônio Pascoal | |
| Author | Santi, Ana Maria Murta | |
| Author | Oliveira, Edward José de | |
| Author | Guimarães, Pedro Pires Goulart | |
| Author | Carvalho, Andrea Teixeira de | |
| Author | Murta, Silvane Maria Fonseca | |
| Author | Pascoal, Vanessa Peruhype Magalhães | |
| Author | Souza-Fagundes, Elaine Maria | |
| Access date | 2025-01-07T16:51:52Z | |
| Available date | 2025-01-07T16:51:52Z | |
| Document date | 2024 | |
| Citation | RIBEIRO, Juliana Martins et al. Can letrozole be repurposed for the treatment of visceral leishmaniasis? Antimicrob Agents Chemother, v. 68, n. 11, e0075624, 2024. | en_US |
| ISSN | 0066-4804 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/67931 | |
| Language | eng | en_US |
| Publisher | American Society for Microbiology | en_US |
| Rights | restricted access | |
| Title | Can letrozole be repurposed for the treatment of visceral leishmaniasis? | en_US |
| Type | Article | |
| DOI | 10.1128/aac.00756-24 | |
| Abstract | Visceral leishmaniasis, caused by Leishmania infantum in New World countries, is the most serious and potentially fatal form of leishmaniasis, if left untreated. There are currently no effective prophylactic measures, and therapeutic options are limited. Therefore, we investigated whether the aromatase inhibitor letrozole (LET), which is already used to treat breast cancer, has an antileishmanial activity and/or immunomodulatory potential and therefore may be used to treat L. infantum infection. LET was active against L. infantum promastigote and amastigote life cycle stages in an in vitro infection model using human THP-1 cell-derived macrophages. In human peripheral blood leukocytes ex vivo, LET reduced the internalized forms of L. infantum by classical monocytes and activated neutrophils. Concomitantly, LET stimulated the production of IL-12/TNF-α and decreased the production of IL-10/TGF-β by peripheral blood phagocytes, while in T and B cells, it promoted the production of TNF-α/IFN-γ and decreased that of IL-10. In a murine infection model, LET significantly reduced the parasite load in the liver after just 5 days and in the spleen after 15 days. During in vivo treatment with LET, the production of TNF-α/IFN-γ also increased. In addition, the proportion of developing granulomas decreased and that of mature granulomas increased in the liver, while there was no significant change in organ architecture in the spleen. Based on these data, repositioning of LET may be promising for the treatment of visceral leishmaniasis in humans. | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brasil. / Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Genômica Funcional de Parasitos. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Pesquisa Clínica e Políticas Públicas em Doenças Infecto-Parasitárias. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Pesquisa Clínica e Políticas Públicas em Doenças Infecto-Parasitárias. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Imunologia Celular e Molecular. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Imunologia de Doenças Virais. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Genômica Funcional de Parasitos. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisa em Biomarcadores. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo de Genômica Funcional de Parasitos. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Grupo Integrado de Pesquisa em Biomarcadores. Belo Horizonte, MG, Brasil. | en_US |
| Affilliation | Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brasil. | en_US |
| Subject | Leishmania infantum | en_US |
| Subject | Chemotherapy | en_US |
| Subject | Drug repositioning | en_US |
| Subject | Human visceral leishmaniasis | en_US |
| Subject | Immunomodulation | en_US |
| Subject | Letrozole | en_US |
| Embargo date | 3100-12-31 | |
