| Author | Silva, Tatiana Araújo | |
| Author | Thomas, Diane | |
| Author | Siqueira Neto, Jair Lage de | |
| Author | Alvarez, Claudia Magalhães Calvet | |
| Access date | 2024-07-16T14:10:01Z | |
| Available date | 2024-07-16T14:10:01Z | |
| Document date | 2024 | |
| Citation | SILVA, Tatiana Araújo et al. Pirfenidone prevents heart fibrosis during chronic Chagas disease cardiomyopathy. International Journal of Molecular Sciences, v. 25, n. 13, p. 1-22, 3 July 2024. | en_US |
| ISSN | 1661-6596 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/65007 | |
| Description | Produção científica do Laboratório de Ultraestrutura Celular. | en_US |
| Sponsorship | This research was funded by an Academic Senate Health Sciences Research Grant, University of California San Diego (RQ276RCALVET ALVAREZ). Tatiana Araújo Silva was supported by scholarships from Fundação Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), with the period abroad funded by the Programa de Doutorado Sanduíche no Exterior (PDSE) from CAPES, edital PDSE2016, process number 88881.135366/2016-01. | en_US |
| Language | eng | en_US |
| Publisher | MDPI | en_US |
| Rights | open access | |
| Title | Pirfenidone prevents heart fibrosis during chronic Chagas disease cardiomyopathy | en_US |
| Type | Article | |
| DOI | 10.3390/ijms25137302 | |
| Abstract | Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF-β (pirfenidone), p38-MAPK (losmapimod) and c-Jun (SP600125) on the modulation of collagen deposition in cardiac fibroblasts (CF) and in vivo models of T. cruzi chronic infection. Sirius Red/Fast Green dye was used to quantify both collagen expression and total protein amount, assessing cytotoxicity. The compounds were also used to treat C57/Bl6 mice chronically infected with T. cruzi, Brazil strain. We identified an anti-fibrotic effect in vitro for pirfenidone (TGF-β inhibitor, IC50 114.3 μM), losmapimod (p38 inhibitor, IC50 17.6 μM) and SP600125 (c-Jun inhibitor, IC50 3.9 μM). This effect was independent of CF proliferation since these compounds do not affect T. cruzi-induced host cell multiplication as measured by BrdU incorporation. Assays of chronic infection of mice with T. cruzi have shown a reduction in heart collagen by pirfenidone. These results propose a novel approach to fibrosis therapy in CD, with the prospect of repurposing pirfenidone to prevent the onset of ECM accumulation in the hearts of the patients. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil. | en_US |
| Affilliation | University of California San Diego. Skaggs School of Pharmacy and Pharmaceutical Sciences. Center for Discovery and Innovation in Parasitic Diseases. La Jolla, CA, USA. | en_US |
| Affilliation | University of California San Diego. Skaggs School of Pharmacy and Pharmaceutical Sciences. Center for Discovery and Innovation in Parasitic Diseases. La Jolla, CA, USA. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Ultraestrutura Celular. Rio de Janeiro, RJ, Brasil. | en_US |
| Subject | Heart fibrosis | en_US |
| Subject | Chagas disease | en_US |
| Subject | Pirfenidone | en_US |
| e-ISSN | 1422-0067 | |
