Resveratrol Reverses Functional Chagas Heart Disease in Mice.
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 dy...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2016-10-01
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| Series: | PLoS Pathogens |
| Online Access: | https://doi.org/10.1371/journal.ppat.1005947 |
| _version_ | 1819133127237304320 |
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| author | Glaucia Vilar-Pereira Vitor C Carneiro Hilton Mata-Santos Amanda R R Vicentino Isalira P Ramos Naira L L Giarola Daniel F Feijó José R Meyer-Fernandes Heitor A Paula-Neto Emiliano Medei Marcelo T Bozza Joseli Lannes-Vieira Claudia N Paiva |
| author_facet | Glaucia Vilar-Pereira Vitor C Carneiro Hilton Mata-Santos Amanda R R Vicentino Isalira P Ramos Naira L L Giarola Daniel F Feijó José R Meyer-Fernandes Heitor A Paula-Neto Emiliano Medei Marcelo T Bozza Joseli Lannes-Vieira Claudia N Paiva |
| author_sort | Glaucia Vilar-Pereira |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T09:42:21Z |
| format | Article |
| id | doaj.art-620113a7b3334c11a095afab687e175b |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-22T09:42:21Z |
| publishDate | 2016-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-620113a7b3334c11a095afab687e175b2022-12-21T18:30:38ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742016-10-011210e100594710.1371/journal.ppat.1005947Resveratrol Reverses Functional Chagas Heart Disease in Mice.Glaucia Vilar-PereiraVitor C CarneiroHilton Mata-SantosAmanda R R VicentinoIsalira P RamosNaira L L GiarolaDaniel F FeijóJosé R Meyer-FernandesHeitor A Paula-NetoEmiliano MedeiMarcelo T BozzaJoseli Lannes-VieiraClaudia N PaivaChronic 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.https://doi.org/10.1371/journal.ppat.1005947 |
| spellingShingle | Glaucia Vilar-Pereira Vitor C Carneiro Hilton Mata-Santos Amanda R R Vicentino Isalira P Ramos Naira L L Giarola Daniel F Feijó José R Meyer-Fernandes Heitor A Paula-Neto Emiliano Medei Marcelo T Bozza Joseli Lannes-Vieira Claudia N Paiva Resveratrol Reverses Functional Chagas Heart Disease in Mice. PLoS Pathogens |
| title | 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_short | Resveratrol Reverses Functional Chagas Heart Disease in Mice. |
| title_sort | resveratrol reverses functional chagas heart disease in mice |
| url | https://doi.org/10.1371/journal.ppat.1005947 |
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