ArticlePLoS pathogens2016
Resveratrol Reverses Functional Chagas Heart Disease in Mice.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Anti-inflammatory and antioxidant therapies for chagasic myocarditis: a systematic review.Parasitology · 2020Pooled it
- Pooled it
- Effects of resveratrol supplementation on cardiac remodeling in hypertensive patients: a randomized controlled clinical trial.Hypertension research : official journal of the Japanese Society of Hypertension · 2023Trial
- Biological Activity of Stilbenoids Against Fungal, Parasitic, and Viral Pathogens.Molecules (Basel, Switzerland) · 2026Review
- Trypanocidal Activity of Dual Redox-Active Quinones:Pathogens (Basel, Switzerland) · 2025Article
- Interventions for Neglected Diseases Caused by Kinetoplastid Parasites: A One Health Approach to Drug Discovery, Development, and Deployment.Pharmaceuticals (Basel, Switzerland) · 2025Review
- System-based insights into parasitological and clinical treatment failure in Chagas disease.mSystems · 2025Review
- Cardiac and Digestive Forms of Chagas Disease: An Update on Pathogenesis, Genetics, and Therapeutic Targets.Mediators of inflammation · 2025Review
- Heart function enhancement by an Nrf2-activating antioxidant in acute Y-strain Chagas disease, but not in chronic Colombian or Y-strain.PLoS neglected tropical diseases · 2024Article
- The intersection of hostMicrobiology and molecular biology reviews : MMBR · 2024Review
- Small molecule mediators of host-T. cruzi-environment interactions in Chagas disease.PLoS pathogens · 2024Review
- Cardiac Abnormalities in a Predictive Mouse Model of Chagas Disease.Pathogens (Basel, Switzerland) · 2023Article
- Inflammation and mitochondria in the pathogenesis of chronic Chagas disease cardiomyopathy.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Resveratrol againstTropical medicine and infectious disease · 2023Article
- Genome-Wide Screening Identifies Gene AKR1C1 Critical for Resistance to Pirarubicin in Bladder Cancer.Cancers · 2023Article
- Antimicrobial Peptides (AMPs): Potential Therapeutic Strategy against Trypanosomiases?Biomolecules · 2023Review
- Cardiomyocyte infection byFrontiers in cellular and infection microbiology · 2023Article
- Signature of cardiac alterations in early and late chronic infections with Trypanosoma cruzi in mice.PloS one · 2023Article
- Resveratrol-like Compounds as SIRT1 Activators.International journal of molecular sciences · 2022Article
- Nitric oxide in parasitic infections: a friend or foe?Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2022Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.