Silva, T.A.; Thomas, D.; Siqueira-Neto, J.L.; Calvet, C.M. Pirfenidone Prevents the Onset of Heart Fibrosis during Chronic Chagas Disease Cardiomyopathy. Preprints2023, 2023111198. https://doi.org/10.20944/preprints202311.1198.v1
APA Style
Silva, T.A., Thomas, D., Siqueira-Neto, J.L., & Calvet, C.M. (2023). Pirfenidone Prevents the Onset of Heart Fibrosis during Chronic Chagas Disease Cardiomyopathy. Preprints. https://doi.org/10.20944/preprints202311.1198.v1
Chicago/Turabian Style
Silva, T.A., Jair Lage Siqueira-Neto and Claudia Magalhaes Calvet. 2023 "Pirfenidone Prevents the Onset of Heart Fibrosis during Chronic Chagas Disease Cardiomyopathy" Preprints. https://doi.org/10.20944/preprints202311.1198.v1
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- (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 is 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 heart of the patients.
Keywords
Heart fibrosis; Chagas disease; Pirfenidone
Subject
Biology and Life Sciences, Parasitology
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.
