Resveratrol Reverses Functional Chagas Heart Disease in Mice
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| DOI: | 10.1371/journal.ppat.1005947 |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/18091 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil. |
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Pereira, Glaucia VilarCarneiro, Vitor C.Santos, Hilton MataVicentino, Amanda R. R.Ramos, Isalira P.Giarola, Naira L. L.Feijó, Daniel F.Fernandes, José R. MeyerPaula Neto, Heitor A.Medei, EmilianoBozza, Marcelo T.Vieira, Joseli LannesPaiva, Claudia N.2017-03-21T12:18:18Z2017-03-21T12:18:18Z2016PEREIRA, Glaucia Vilar; et al. Resveratrol Reverses Functional Chagas Heart Disease in Mice. PLoS Pathog, v.12, n.10, e1005947, 19p, Oct. 2016.1553-7366https://www.arca.fiocruz.br/handle/icict/1809110.1371/journal.ppat.10059471553-7374engPublic Library of ScienceCardiomiopatia chagásica crônicaRatosResveratrolChronic chagasic cardiomyopathyMiceResveratrolResveratrol Reverses Functional Chagas Heart Disease in Miceinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis, Programa de Biologia Molecular e Tecnologia, Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Análises Clínicas e Toxicológicas.Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis, Programa de Biologia Molecular e Tecnologia, Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Hospital Universitário Clementino Fraga Filho. Departamento de Radiologia, Rio de Janeiro, RJ, Brasil / Univerisdade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Centro Nacional de Biologia Estrutural e Bioimagem, Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis, Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Bioquímica Médica Leopoldo de Meis, Rio de Janeiro, RJ, Brasil / Instituto Nacional de Ciência e Tecnologia da Biologia Estrutural e Bioimagem, Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Fármacos. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Centro Nacional de Biologia Estrutural e Bioimagem. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.undação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Imunologia. Rio de Janeiro, RJ, Brasil.Chronic chagasic cardiomyopathy (CCC) develops years after acute infection by Trypanosoma cruzi and does not improve after trypanocidal therapy, despite reduction of parasite burden. During disease, the heart undergoes oxidative stress, a potential causative factor for arrhythmias and contractile dysfunction. Here we tested whether antioxidants/ cardioprotective drugs could improve cardiac function in established Chagas heart disease. We chose a model that resembles B1-B2 stage of human CCC, treated mice with resveratrol and performed electrocardiography and echocardiography studies. Resveratrol reduced the prolonged PR and QTc intervals, increased heart rates and reversed sinus arrhythmia, atrial and atrioventricular conduction disorders; restored a normal left ventricular ejection fraction, improved stroke volume and cardiac output. Resveratrol activated the AMPK-pathway and reduced both ROS production and heart parasite burden, without interfering with vascularization or myocarditis intensity. Resveratrol was even capable of improving heart function of infected mice when treatment was started late after infection, while trypanocidal drug benznidazole failed. We attempted to mimic resveratrol's actions using metformin (AMPK-activator) or tempol (SOD-mimetic). Metformin and tempol mimicked the beneficial effects of resveratrol on heart function and decreased lipid peroxidation, but did not alter parasite burden. These results indicate that AMPK activation and ROS neutralization are key strategies to induce tolerance to Chagas heart disease. Despite all tissue damage observed in established Chagas heart disease, we found that a physiological dysfunction can still be reversed by treatment with resveratrol, metformin and tempol, resulting in improved heart function and representing a starting point to develop innovative therapies in CCC.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/18091/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALglaucia_pereira_etal_IOC_2016.pdfglaucia_pereira_etal_IOC_2016.pdfapplication/pdf4545847https://www.arca.fiocruz.br/bitstream/icict/18091/2/glaucia_pereira_etal_IOC_2016.pdfa4ddfd0cf63ee363ce0dafdc209a732dMD52TEXTglaucia_pereira_etal_IOC_2016.pdf.txtglaucia_pereira_etal_IOC_2016.pdf.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
Resveratrol Reverses Functional Chagas Heart Disease in Mice |
| title |
Resveratrol Reverses Functional Chagas Heart Disease in Mice |
| spellingShingle |
Resveratrol Reverses Functional Chagas Heart Disease in Mice Pereira, Glaucia Vilar Cardiomiopatia chagásica crônica Ratos Resveratrol Chronic chagasic cardiomyopathy Mice Resveratrol |
| title_short |
Resveratrol Reverses Functional Chagas Heart Disease in Mice |
| title_full |
Resveratrol Reverses Functional Chagas Heart Disease in Mice |
| title_fullStr |
Resveratrol Reverses Functional Chagas Heart Disease in Mice |
| title_full_unstemmed |
Resveratrol Reverses Functional Chagas Heart Disease in Mice |
| title_sort |
Resveratrol Reverses Functional Chagas Heart Disease in Mice |
| author |
Pereira, Glaucia Vilar |
| author_facet |
Pereira, Glaucia Vilar Carneiro, Vitor C. Santos, Hilton Mata Vicentino, Amanda R. R. Ramos, Isalira P. Giarola, Naira L. L. Feijó, Daniel F. Fernandes, José R. Meyer Paula Neto, Heitor A. Medei, Emiliano Bozza, Marcelo T. Vieira, Joseli Lannes Paiva, Claudia N. |
| author_role |
author |
| author2 |
Carneiro, Vitor C. Santos, Hilton Mata Vicentino, Amanda R. R. Ramos, Isalira P. Giarola, Naira L. L. Feijó, Daniel F. Fernandes, José R. Meyer Paula Neto, Heitor A. Medei, Emiliano Bozza, Marcelo T. Vieira, Joseli Lannes Paiva, Claudia N. |
| author2_role |
author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Pereira, Glaucia Vilar Carneiro, Vitor C. Santos, Hilton Mata Vicentino, Amanda R. R. Ramos, Isalira P. Giarola, Naira L. L. Feijó, Daniel F. Fernandes, José R. Meyer Paula Neto, Heitor A. Medei, Emiliano Bozza, Marcelo T. Vieira, Joseli Lannes Paiva, Claudia N. |
| dc.subject.other.pt_BR.fl_str_mv |
Cardiomiopatia chagásica crônica Ratos Resveratrol |
| topic |
Cardiomiopatia chagásica crônica Ratos Resveratrol Chronic chagasic cardiomyopathy Mice Resveratrol |
| dc.subject.en.pt_BR.fl_str_mv |
Chronic chagasic cardiomyopathy Mice Resveratrol |
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Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia das Interações. Rio de Janeiro, RJ. Brasil. |
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2016 |
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2016 |
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2017-03-21T12:18:18Z |
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2017-03-21T12:18:18Z |
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PEREIRA, Glaucia Vilar; et al. Resveratrol Reverses Functional Chagas Heart Disease in Mice. PLoS Pathog, v.12, n.10, e1005947, 19p, Oct. 2016. |
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https://www.arca.fiocruz.br/handle/icict/18091 |
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1553-7366 |
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10.1371/journal.ppat.1005947 |
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1553-7374 |
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PEREIRA, Glaucia Vilar; et al. Resveratrol Reverses Functional Chagas Heart Disease in Mice. PLoS Pathog, v.12, n.10, e1005947, 19p, Oct. 2016. 1553-7366 10.1371/journal.ppat.1005947 1553-7374 |
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