Cardioprotective Effect of Empagliflozin in Rats with IsoproterenolInduced Myocardial Infarction: Evaluation of Lipid Profile, Oxidative Stress, Inflammation, DNA Damage, and Apoptosis

Abstract

—The antidiabetic drug empagliflozin is reported to have many cardioprotective effects. However, no studies have investigated the protective effects of empagliflozin (EMPA) in isoprenaline (ISO)-induced cardiac oxidative damage-a model mimicking the harmful effects of excess catecholamines on the heart. Therefore, in this study, we aimed to reveal the protective effect of EMPA in isoproterenol ISO-induced myocardial infarction in rats. We induced myocardial infarction by subcutaneously injecting ISO (100 mg/kg). To determine the protective effects of EMPA on the myocardial damage, we administered two different doses (10 and 20 mg/kg) by gavage for 14 days. Here we have shown that a 20 mg/kg dose of EMPA completely rescues rats from myocardial infarction by normalizing the following: elevated ST-segment, increased heart rate, decreased R amplitude, prolongation of the QT interval, and shortened RR interval. In addition, EMPA (20 mg/kg) ameliorates ISO-induced changes in serum cTnI, CK, ischemia-modified albumin (IMA), LDH, AST, ALT levels, and heart index. It improves serum lipid profile by decreasing cholesterol, triglycerides, LDL, and VLDL levels, and by increasing HDL levels. Moreover, EMPA (20 mg/kg) alleviates increased myocardial oxidative stress and inflammation by decreasing MDA, TNF-α, and IL-6 levels and increasing SOD and GPx levels. Furthermore, 20 mg/kg EMPA leads to reductions in DNA damage and apoptosis by downregulating of 8-OHdG and caspase-3 expressions. Collectively, EMPA exerts its protective effects on myocardial damage by improving oxidative stress, apoptosis, lipid profile and oxidative DNA damage in ISO-induced experimental myocardial infarction in rats.