ArticleAntioxidants (Basel, Switzerland)2020
Antiarrhythmic Effects of Melatonin and Omega-3 Are Linked with Protection of Myocardial Cx43 Topology and Suppression of Fibrosis in Catecholamine Stressed Normotensive and Hypertensive Rats.
Article in Antioxidants (Basel, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 39 citations in OpenAlex.
- Connexin43 Deficiency Leads to Ventricular Arrhythmias by Reprogramming Proline Metabolism.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Metabolic reprogramming in cardiac fibrosis: mechanisms, crosstalk, and therapeutic interventions.Frontiers in physiology · 2026Review
- Association Between Melatonin Receptor Agonists and Cardiac Arrhythmia; Disproportionality Analysis Studies Using Pharmacovigilance Databases.Cardiovascular toxicology · 2025Article
- Isoproterenol mechanisms in inducing myocardial fibrosis and its application as an experimental model for the evaluation of therapeutic potential of phytochemicals and pharmaceuticals.Animal models and experimental medicine · 2025Review
- Inflammation pathways as therapeutic targets in angiotensin II induced atrial fibrillation.Frontiers in pharmacology · 2025Review
- Effects of renal denervation on the course of cardiorenal syndrome: insight from studies with fawn-hooded hypertensive rats.Physiological research · 2024Article
- Article
- Association between inflammation markers and all-cause mortality in critical ill patients with atrial fibrillation: Analysis of the Multi-Parameter Intelligent Monitoring in Intensive Care (MIMIC-IV) database.International journal of cardiology. Heart & vasculature · 2024Article
- Connexin43, A Promising Target to Reduce Cardiac Arrhythmia Burden in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2024Review
- Melatonin enhances captopril mediated cardioprotective effects and improves mitochondrial dynamics in male Wistar rats with chronic heart failure.Scientific reports · 2024Article
- The Role of Omega-3 in Attenuating Cardiac Remodeling and Heart Failure through the Oxidative Stress and Inflammation Pathways.Antioxidants (Basel, Switzerland) · 2023Review
- The treatment with trandolapril and losartan attenuates pressure and volume overload alternations of cardiac connexin-43 and extracellular matrix in Ren-2 transgenic rats.Scientific reports · 2023Article
- Impact of Impaired Kidney Function on Arrhythmia-Promoting Cardiac Ion Channel Regulation.International journal of molecular sciences · 2023Review
- Blockade of Melatonin Receptors Abolishes Its Antiarrhythmic Effect and Slows Ventricular Conduction in Rat Hearts.International journal of molecular sciences · 2023Article
- Distinct Cardiac Connexin-43 Expression in Hypertrophied and Atrophied Myocardium May Impact the Vulnerability of the Heart to Malignant Arrhythmias. A Pilot Study.Physiological research · 2023Article
- Melatonin increases collagen content accumulation and Fibroblast Growth Factor-2 secretion in cultured human cardiac fibroblasts.Pharmacological reports : PR · 2023Article
- Mitochondrial Connexins and Mitochondrial Contact Sites with Gap Junction Structure.International journal of molecular sciences · 2023Review
- Hypertension Induces Pro-arrhythmic Cardiac Connexome Disorders: Protective Effects of Treatment.Biomolecules · 2023Review
- Anti-Fibrotic Potential of Angiotensin (1-7) in Hemodynamically Overloaded Rat Heart.International journal of molecular sciences · 2023Article
- Cardiac Cx43 Signaling Is Enhanced and TGF-β1/SMAD2/3 Suppressed in Response to Cold Acclimation and Modulated by Thyroid Status in Hairless SHRBiomedicines · 2022Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 4 countries.
Funding
Abstract
Cardiac β-adrenergic overstimulation results in oxidative stress, hypertrophy, ischemia, lesion, and fibrosis rendering the heart vulnerable to malignant arrhythmias. We aimed to explore the anti-arrhythmic efficacy of the anti-oxidative and anti-inflammatory compounds, melatonin, and omega-3, and their mechanisms of actions in normotensive and hypertensive rats exposed to isoproterenol (ISO) induced β-adrenergic overdrive. Eight-month-old, male SHR, and Wistar rats were injected during 7 days with ISO (cumulative dose, 118 mg/kg). ISO rats were either untreated or concomitantly treated with melatonin (10 mg/kg/day) or omega-3 (Omacor, 1.68 g/kg/day) until 60 days of ISO withdrawal and compared to non-ISO controls. Findings showed that both melatonin and omega-3 increased threshold current to induce ventricular fibrillation (VF) in ISO rats regardless of the strain. Prolonged treatment with these compounds resulted in significant suppression of ISO-induced extracellular matrix alterations, as indicated by reduced areas of diffuse fibrosis and decline of hydroxyproline, collagen-1, SMAD2/3, and TGF-β1 protein levels. Importantly, the highly pro-arrhythmic ISO-induced disordered cardiomyocyte distribution of electrical coupling protein, connexin-43 (Cx43), and its remodeling (lateralization) were significantly attenuated by melatonin and omega-3 in Wistar as well as SHR hearts. In parallel, both compounds prevented the post-ISO-related increase in Cx43 variant phosphorylated at serine 368 along with PKCε, which are known to modulate Cx43 remodeling. Melatonin and omega-3 increased SOD1 or SOD2 protein levels in ISO-exposed rats of both strains. Altogether, the results indicate that anti-arrhythmic effects of melatonin and omega-3 might be attributed to the protection of myocardial Cx43 topology and suppression of fibrosis in the setting of oxidative stress induced by catecholamine overdrive in normotensive and hypertensive rats.
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Registered trials
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