Dapagliflozin Treatment Improves Cardiac Remodeling and Dysfunction in Heart Failure Induced Rats

Abstract

Background: Sodium-glucose cotransporter-2 (SGLT-2) inhibitor dapagliflozin is a novel antihyperglycemic drug that has cardioprotective effects. It has been shown to minimize the incidence of cardiovascular mortality and heart failure (HF) hospitalization. Furthermore, these benefits may remain regardless of the existence of diabetes. However, the mechanisms by which dapagliflozin mediates these effects in HF patient are unknown, and its efficacy and practical use are still debatable. Objectives: to assess the therapeutic effect of dapagliflozin on rat with experimentally induced HF and its possible underlying mechanism of action. Methods: The left anterior descending (LAD) coronary artery was ligated in rats to induce HF. Dapagliflozin (1 mg/kg/day) was given by gavage for four weeks. Heart weight (HW), Body weight (BW), blood pressure, heart rate (HR), fasting serum glucose, insulin, glycated hemoglobin A1C (HbA1c), cardiac injury markers [creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), lactate dehydrogenase (LDH)], markers of fibrosis [transforming growth factor beta 1 (TGF-β1), procollagen I C-terminal propeptide (PICP), procollagen III N-terminal peptide (PIIINT)], mediators of inflamation [tumor necrosis factor-alpha (TNF-α)], markers of oxidative stress [super oxide dismutase (SOD) and malondialdehyde (MDA)] and mediators of apoptosis (caspase 3 and BCL-2) were assessed. Histopathological examinations were performed using hematoxylin and eosin (H & E) for the heart, lung, and liver, and masson trichrome for heart. Results: Dapagliflozin decreased HW, HW/BW, cardiac injury markers, markers of fibrosis, mediators of inflammation, MDA and cardiac level of Caspase 3, while increased levels of SOD and BCL-2 in HF-induced rats. Dapagliflozin also improved the histopathological picture of heart, liver and lung. Conclusion: Dapagliflozin attenuated fibrosis, inflammation, oxidative stress, and apoptosis in HF-induced rats, thereby alleviating myocardial remodeling and dysfunction. Dapagliflozin alleviated histopathological changes in the hearts, lungs, and livers.