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

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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.

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ACKNOWLEDGMENTS

We thank Amanda Chilaka (microbiologist at the Whitehead Institute in Boston) for language editing of the manuscript.

Funding

This research was supported by Sivas Cumhuriyet University Scientific Research Projects Commission as research project no. V-092.

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Authors and Affiliations

  1. Department of Veterinary Physiology, Faculty of Veterinary Medicine, Sivas Cumhuriyet University, 58140, Sivas, Turkey

    Mehmet Ekici & Mustafa Koҫkaya

  2. Department of Veterinary Pharmacology and Toxicology, Faculty of Veterinary Medicine, Sivas Cumhuriyet University, 58140, Sivas, Turkey

    Hüseyin Güngör

  3. Department of Veterinary Pathology, Faculty of Ceyhan Veterinary Medicine, Cukurova University, 01330, Adana, Turkey

    Mehmet Önder Karayığıt

  4. Department of Pharmacology, Faculty of Pharmacy, Izmir Katip Celebi University, 35620, Izmir, Turkey

    Nergiz Hacer Turgut

  5. Department of Veterinary Pathology, Faculty of Veterinary Medicine, Sivas Cumhuriyet University, 58140, Sivas, Turkey

    Özhan Karataș

  6. Department of Endocrinology, Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, 02215, Boston, MA, USA

    Aykut Göktürk Üner

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Mehmet Ekici, Güngör, H., Karayığıt, M.Ö. et al. Cardioprotective Effect of Empagliflozin in Rats with Isoproterenol-Induced Myocardial Infarction: Evaluation of Lipid Profile, Oxidative Stress, Inflammation, DNA Damage, and Apoptosis. Biol Bull Russ Acad Sci 49 (Suppl 1), S159–S172 (2022). https://doi.org/10.1134/S1062359022130039

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