{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:24:48Z","timestamp":1791296688977,"version":"4.1.0"},"reference-count":51,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T00:00:00Z","timestamp":1477526400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"DOI":"10.1371\/journal.ppat.1005947","type":"journal-article","created":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T13:43:27Z","timestamp":1477575807000},"page":"e1005947","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":77,"title":["Resveratrol Reverses Functional Chagas Heart Disease in Mice"],"prefix":"10.1371","volume":"12","author":[{"given":"Glaucia","family":"Vilar-Pereira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vitor C.","family":"Carneiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hilton","family":"Mata-Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda R. R.","family":"Vicentino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3577-0403","authenticated-orcid":true,"given":"Isalira P.","family":"Ramos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5986-4861","authenticated-orcid":true,"given":"Naira L. L.","family":"Giarola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel F.","family":"Feij\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 R.","family":"Meyer-Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heitor A.","family":"Paula-Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emiliano","family":"Medei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo T.","family":"Bozza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseli","family":"Lannes-Vieira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia N.","family":"Paiva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,10,27]]},"reference":[{"issue":"6071","key":"ref1","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1126\/science.1214935","article-title":"Disease tolerance as a defense strategy","volume":"335","author":"R Medzhitov","year":"2012","journal-title":"Science"},{"issue":"6137","key":"ref2","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1126\/science.1233632","article-title":"Role of tissue protection in lethal respiratory viral-bacterial coinfection","volume":"340","author":"AM Jamieson","year":"2013","journal-title":"Science"},{"issue":"1","key":"ref3","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.tem.2014.11.001","article-title":"Is AMPK the savior of the failing heart?","volume":"26","author":"TT Kim","year":"2015","journal-title":"Trends in endocrinology and metabolism: TEM"},{"issue":"2","key":"ref4","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.lfs.2013.12.011","article-title":"Potential of resveratrol in the treatment of heart failure","volume":"95","author":"P Raj","year":"2014","journal-title":"Life sciences"},{"issue":"9","key":"ref5","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1038\/aps.2013.82","article-title":"Resveratrol protects rabbit ventricular myocytes against oxidative stress-induced arrhythmogenic activity and Ca2+ overload","volume":"34","author":"W Li","year":"2013","journal-title":"Acta pharmacologica Sinica"},{"issue":"2\u20133","key":"ref6","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.ejphar.2006.10.016","article-title":"In vitro electrophysiological mechanisms for antiarrhythmic efficacy of resveratrol, a red wine antioxidant","volume":"554","author":"WP Chen","year":"2007","journal-title":"European journal of pharmacology"},{"issue":"4","key":"ref7","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1016\/j.bbrc.2005.12.124","article-title":"Resveratrol, a natural ingredient of grape skin: antiarrhythmic efficacy and ionic mechanisms","volume":"340","author":"Y Zhang","year":"2006","journal-title":"Biochemical and biophysical research communications"},{"issue":"1","key":"ref8","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1111\/bph.12409","article-title":"Characterization of a novel multifunctional resveratrol derivative for the treatment of atrial fibrillation","volume":"171","author":"I Baczko","year":"2014","journal-title":"British journal of pharmacology"},{"issue":"1\u20133","key":"ref9","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.ejphar.2010.09.036","article-title":"Favorable effects of resveratrol on sympathetic neural remodeling in rats following myocardial infarction","volume":"649","author":"P Xin","year":"2010","journal-title":"European journal of pharmacology"},{"issue":"6","key":"ref10","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.bbadis.2015.01.014","article-title":"The pharmacology of resveratrol in animals and humans","volume":"1852","author":"EJ Park","year":"2015","journal-title":"Biochimica et biophysica acta"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"683230","DOI":"10.1155\/2014\/683230","article-title":"Chagas disease cardiomyopathy: immunopathology and genetics","volume":"2014","author":"E Cunha-Neto","year":"2014","journal-title":"Mediators of inflammation"},{"issue":"9723","key":"ref12","doi-asserted-by":"crossref","first-page":"1388","DOI":"10.1016\/S0140-6736(10)60061-X","article-title":"Chagas disease","volume":"375","author":"A Rassi Jr.","year":"2010","journal-title":"Lancet"},{"issue":"4","key":"ref13","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1002\/path.2975","article-title":"NADPH oxidase inhibition ameliorates Trypanosoma cruzi-induced myocarditis during Chagas disease","volume":"225","author":"M Dhiman","year":"2011","journal-title":"The Journal of pathology"},{"issue":"6","key":"ref14","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s10863-008-9184-4","article-title":"Mitochondrial generation of reactive oxygen species is enhanced at the Q(o) site of the complex III in the myocardium of Trypanosoma cruzi-infected mice: beneficial effects of an antioxidant","volume":"40","author":"JJ Wen","year":"2008","journal-title":"Journal of bioenergetics and biomembranes"},{"issue":"22","key":"ref15","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1016\/j.jacc.2010.02.030","article-title":"Phenyl-alpha-tert-butyl-nitrone and benzonidazole treatment controlled the mitochondrial oxidative stress and evolution of cardiomyopathy in chronic chagasic Rats","volume":"55","author":"JJ Wen","year":"2010","journal-title":"Journal of the American College of Cardiology"},{"issue":"3","key":"ref16","doi-asserted-by":"crossref","first-page":"e0003659","DOI":"10.1371\/journal.pntd.0003659","article-title":"Pentoxifylline Reverses Chronic Experimental Chagasic Cardiomyopathy in Association with Repositioning of Abnormal CD8+ T-Cell Response","volume":"9","author":"IR Pereira","year":"2015","journal-title":"PLoS neglected tropical diseases"},{"issue":"4","key":"ref17","doi-asserted-by":"crossref","first-page":"1521","DOI":"10.1128\/AAC.49.4.1521-1528.2005","article-title":"Treatment with benznidazole during the chronic phase of experimental Chagas disease decreases cardiac alterations","volume":"49","author":"S Garcia","year":"2005","journal-title":"Antimicrobial agents and chemotherapy"},{"issue":"4","key":"ref18","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/j.1742-7843.2006.pto_253.x","article-title":"Treatment of experimental chronic chagas disease with trifluralin","volume":"98","author":"A Zaidenberg","year":"2006","journal-title":"Basic & clinical pharmacology & toxicology"},{"issue":"10","key":"ref19","doi-asserted-by":"crossref","first-page":"724","DOI":"10.7326\/0003-4819-144-10-200605160-00006","article-title":"Long-term cardiac outcomes of treating chronic Chagas disease with benznidazole versus no treatment: a nonrandomized trial","volume":"144","author":"R Viotti","year":"2006","journal-title":"Annals of internal medicine"},{"issue":"20","key":"ref20","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1056\/NEJMoa1313122","article-title":"Randomized trial of posaconazole and benznidazole for chronic Chagas disease","volume":"370","author":"I Molina","year":"2014","journal-title":"The New England journal of medicine"},{"key":"ref21","article-title":"Randomized Trial of Benznidazole for Chronic Chagas Cardiomyopathy","author":"CA Morillo","year":"2015","journal-title":"The New England journal of medicine"},{"issue":"2","key":"ref22","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.ccep.2015.03.016","article-title":"Arrhythmias in Chagasic Cardiomyopathy","volume":"7","author":"C Healy","year":"2015","journal-title":"Card Electrophysiol Clin"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/B978-0-12-385863-4.00003-4","article-title":"Cell-based therapy in Chagas disease","volume":"75","author":"AC de Carvalho","year":"2011","journal-title":"Advances in parasitology"},{"issue":"7","key":"ref24","doi-asserted-by":"crossref","first-page":"2531","DOI":"10.1172\/JCI58525","article-title":"Oxidative stress fuels Trypanosoma cruzi infection in mice","volume":"122","author":"CN Paiva","year":"2012","journal-title":"The Journal of clinical investigation"},{"issue":"6","key":"ref25","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1089\/ars.2013.5447","article-title":"Are reactive oxygen species always detrimental to pathogens?","volume":"20","author":"CN Paiva","year":"2014","journal-title":"Antioxidants & redox signaling"},{"issue":"10","key":"ref26","doi-asserted-by":"crossref","first-page":"25234","DOI":"10.3390\/ijms161025234","article-title":"Diabetic Cardiovascular Disease Induced by Oxidative Stress","volume":"16","author":"Y Kayama","year":"2015","journal-title":"International journal of molecular sciences"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"272","DOI":"10.4269\/ajtmh.1964.13.272","article-title":"Chronic and Progressive Myocarditis and Myositis in C3h Mice Infected with Trypanosoma Cruzi","volume":"13","author":"EE Federici","year":"1964","journal-title":"The American journal of tropical medicine and hygiene"},{"issue":"4","key":"ref28","first-page":"287","article-title":"Electrocardiographic changes in chronic Trypanosoma cruzi infected Cebus apella monkeys","volume":"56","author":"CA Falasca","year":"1991","journal-title":"Arquivos brasileiros de cardiologia"},{"issue":"Pt 6","key":"ref29","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1017\/S0031182006001193","article-title":"Characterization of cardiopulmonary function and cardiac muscarinic and adrenergic receptor density adaptation in C57BL\/6 mice with chronic Trypanosoma cruzi infection","volume":"133","author":"NN Rocha","year":"2006","journal-title":"Parasitology"},{"issue":"10","key":"ref30","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/nrcardio.2012.109","article-title":"Diagnosis and management of Chagas disease and cardiomyopathy","volume":"9","author":"AL Ribeiro","year":"2012","journal-title":"Nature reviews Cardiology"},{"issue":"2","key":"ref31","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.jconrel.2011.09.083","article-title":"Administration of resveratrol: What formulation solutions to bioavailability limitations?","volume":"158","author":"A Amri","year":"2012","journal-title":"J Control Release"},{"issue":"8","key":"ref32","doi-asserted-by":"crossref","first-page":"e0003945","DOI":"10.1371\/journal.pntd.0003945","article-title":"Adipose Tissue-Derived Mesenchymal Stromal Cells Protect Mice Infected with Trypanosoma cruzi from Cardiac Damage through Modulation of Anti-parasite Immunity","volume":"9","author":"DB Mello","year":"2015","journal-title":"PLoS neglected tropical diseases"},{"issue":"2","key":"ref33","doi-asserted-by":"crossref","first-page":"e16959","DOI":"10.1371\/journal.pone.0016959","article-title":"Aspirin treatment of mice infected with Trypanosoma cruzi and implications for the pathogenesis of Chagas disease","volume":"6","author":"S Mukherjee","year":"2011","journal-title":"PloS one"},{"issue":"2","key":"ref34","doi-asserted-by":"crossref","first-page":"207","DOI":"10.4269\/ajtmh.1999.61.207","article-title":"Application of cardiac gated magnetic resonance imaging in murine Chagas disease","volume":"61","author":"LA Jelicks","year":"1999","journal-title":"The American journal of tropical medicine and hygiene"},{"issue":"3","key":"ref35","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1161\/CIRCULATIONAHA.110.953208","article-title":"Impaired macrophage migration inhibitory factor-AMP-activated protein kinase activation and ischemic recovery in the senescent heart","volume":"122","author":"H Ma","year":"2010","journal-title":"Circulation"},{"issue":"35","key":"ref36","doi-asserted-by":"crossref","first-page":"24194","DOI":"10.1074\/jbc.M802869200","article-title":"Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt","volume":"283","author":"AY Chan","year":"2008","journal-title":"The Journal of biological chemistry"},{"issue":"8","key":"ref37","doi-asserted-by":"crossref","first-page":"1887","DOI":"10.1113\/jphysiol.2014.270101","article-title":"Resveratrol protects against doxorubicin-induced cardiotoxicity in aged hearts through the SIRT1-USP7 axis","volume":"593","author":"TK Sin","year":"2015","journal-title":"The Journal of physiology"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"2192","DOI":"10.1038\/ncomms3192","article-title":"Metformin improves healthspan and lifespan in mice","volume":"4","author":"A Martin-Montalvo","year":"2013","journal-title":"Nature communications"},{"issue":"5","key":"ref39","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.trstmh.2011.01.007","article-title":"Mitochondrial involvement in chronic chagasic cardiomyopathy","volume":"105","author":"A Baez","year":"2011","journal-title":"Transactions of the Royal Society of Tropical Medicine and Hygiene"},{"issue":"4","key":"ref40","first-page":"150","article-title":"Role of mitochondria and reactive oxygen species in the progression of heart failure","volume":"67","author":"G Guzman Mentesana","year":"2010","journal-title":"Rev Fac Cien Med Univ Nac Cordoba"},{"issue":"1","key":"ref41","doi-asserted-by":"crossref","first-page":"H457","DOI":"10.1152\/ajpheart.00002.2007","article-title":"Metformin and phenformin activate AMP-activated protein kinase in the heart by increasing cytosolic AMP concentration","volume":"293","author":"L Zhang","year":"2007","journal-title":"American journal of physiology Heart and circulatory physiology"},{"issue":"3","key":"ref42","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1161\/CIRCRESAHA.108.190918","article-title":"Activation of AMP-activated protein kinase by metformin improves left ventricular function and survival in heart failure","volume":"104","author":"S Gundewar","year":"2009","journal-title":"Circulation research"},{"issue":"2","key":"ref43","doi-asserted-by":"crossref","first-page":"e87140","DOI":"10.1371\/journal.pone.0087140","article-title":"Tempol, an intracellular antioxidant, inhibits tissue factor expression, attenuates dendritic cell function, and is partially protective in a murine model of cerebral malaria","volume":"9","author":"IM Francischetti","year":"2014","journal-title":"PloS one"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.ijbiomac.2016.03.014","article-title":"Resveratrol inhibits Trypanosoma cruzi arginine kinase and exerts a trypanocidal activity","volume":"87","author":"EA Valera Vera","year":"2016","journal-title":"Int J Biol Macromol"},{"issue":"19","key":"ref45","doi-asserted-by":"crossref","first-page":"2568","DOI":"10.1161\/CIRCULATIONAHA.108.798561","article-title":"Metformin prevents progression of heart failure in dogs: role of AMP-activated protein kinase","volume":"119","author":"H Sasaki","year":"2009","journal-title":"Circulation"},{"issue":"1","key":"ref46","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1111\/nyas.12796","article-title":"Direct molecular targets of resveratrol: identifying key interactions to unlock complex mechanisms","volume":"1348","author":"RG Britton","year":"2015","journal-title":"Annals of the New York Academy of Sciences"},{"issue":"7","key":"ref47","doi-asserted-by":"crossref","first-page":"e69452","DOI":"10.1371\/journal.pone.0069452","article-title":"Resveratrol alleviates endotoxin-induced myocardial toxicity via the Nrf2 transcription factor","volume":"8","author":"E Hao","year":"2013","journal-title":"PloS one"},{"issue":"3","key":"ref48","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/j.cell.2012.01.017","article-title":"Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases","volume":"148","author":"SJ Park","year":"2012","journal-title":"Cell"},{"issue":"5","key":"ref49","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.cmet.2012.04.003","article-title":"SIRT1 is required for AMPK activation and the beneficial effects of resveratrol on mitochondrial function","volume":"15","author":"NL Price","year":"2012","journal-title":"Cell metabolism"},{"issue":"4","key":"ref50","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1645\/GE-2396.1","article-title":"ECG detection of murine chagasic cardiomyopathy","volume":"96","author":"CS Eickhoff","year":"2010","journal-title":"The Journal of parasitology"},{"issue":"8","key":"ref51","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1002\/mnfr.201100117","article-title":"Enhancing the bioavailability of resveratrol by combining it with piperine","volume":"55","author":"JJ Johnson","year":"2011","journal-title":"Molecular nutrition & food research"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.ppat.1005947","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,23]],"date-time":"2018-10-23T01:41:54Z","timestamp":1540258914000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1005947"}},"subtitle":[],"editor":[{"given":"Leda Q","family":"Vieira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,10,27]]},"references-count":51,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2016,10,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1005947","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,10,27]]}}}