الفهرس 
Introduction & Aim of the WorkOnly 14 pages are availabe for public view
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Abstract
Myocardial fibrosis refers to a variety of quantitative and qualitative changes in the interstitial myocardial collagen network that occur in response to cardiac ischemic insults, systemic diseases, drugs, or any other harmful stimulus affecting the circulatory system or the heart itself. Myocardial fibrosis alters the architecture of the myocardium, facilitating the development of cardiac dysfunction, also inducing arrhythmias, influencing the clinical course and outcome of heart failure patients. Focusing on myocardial fibrosis may potentially improve patient care through the targeted diagnosis and treatment of emerging fibrotic pathways.
Gliflozins are Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new drug class approved for treatment of diabetes, which have been shown to possess a favorable metabolic profile and to reduce atherosclerotic events, hospitalization for heart failure, cardiovascular and total mortality, and progression of chronic kidney disease. Although initially considered to be only glucose-lowering agents, the effects of SGLT2i have expanded far beyond that, and their use is now being studied in the treatment of heart failure and chronic kidney disease, even in patients without diabetes.
The current study aimed to investigate the possibility of empagliflozin to exert a protective effect against cardiac fibrosis and dysfunction in animals with normal glycemic conditions. In addition to studying the molecular mechanisms of this effect if present through measuring the expression of profibrotic proteins of TGF-β1/SMAD/JNK1 pathways, and its downstream effectors in heart cells.
To achieve such aims, cardiac fibrosis model was initiated with injections of small daily doses of isoprenaline (5 mg/kg, I.P.) for one month in all groups except the negative control one. Pirfenidone was used as a reference standard at a
Abstract
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dose of (500 mg/kg, P.O.) and empagliflozin was administered orally on three dose levels (5, 10, and 20 mg/kg, P.O.). All treatments started 14 days before isoprenaline insult, and continued for one month with isoprenaline.
Histopathological examination of left ventricle and heart weight changes were evaluated. Cardiac markers (CK-MB, and troponin) were measured. Additionally, cardiac concentrations of TGF-β1, JNK, TNF-α, and MCP-1 were measured, along with immunohistochemical evaluation of cardiac NFκ-B, and α-SMA. Expression of SMADs, fibronectin, CTGF, and collagens was evaluated by PCR in cardiac tissues.
Isoprenaline insulted groups showed deterioration in all measured parameters with regard to control group. Treatment with empagliflozin ameliorated these anomalies with greater protection induced by higher dosing in a manner comparable to this achieved with pirfenidone. These current results demonstrated empagliflozin as a potential cardioprotective agent against myocardial fibrosis which represents a novel promising approach to the fight against cardiac dysfunction by elucidating new mechanisms involved in establishing such effect.