Empagliflozin Significantly Prevents the Doxorubicin-induced Acute Cardiotoxicity via Non-antioxidant Pathways

• Published in: Cardiovascular toxicology Vol. 21; no. 9; pp. 747 - 758
• Main Authors: Barış, Veysel Özgür, Dinçsoy, Adnan Berk, Gedikli, Esra, Zırh, Selim, Müftüoğlu, Sevda, Erdem, Ayşen
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.09.2021; Springer; Springer Nature B.V
• Subjects: Action Potentials - drug effects; Animals; Antimitotic agents; Antineoplastic agents; Antioxidants; Benzhydryl Compounds - pharmacology; Biomedical and Life Sciences; Biomedicine; Body weight; Cardiology; Cardiotoxicity; Cell growth; Cell morphology; Cell proliferation; Cell Proliferation - drug effects; Cytology; Diabetes mellitus; Disease Models, Animal; Doxorubicin; Ethylenediaminetetraacetic acid; Glucosides - pharmacology; Heart Diseases - chemically induced; Heart Diseases - pathology; Heart Diseases - physiopathology; Heart Diseases - prevention & control; Heart Rate - drug effects; Male; Methylene blue; Mitochondria, Heart - drug effects; Mitochondria, Heart - metabolism; Mitochondria, Heart - ultrastructure; Morphology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - ultrastructure; Pharmacology/Toxicology; Rats; Rats, Sprague-Dawley; Sodium-Glucose Transporter 2 Inhibitors - pharmacology; Stroke Volume - drug effects; Ventricular Function, Left - drug effects; Heart failure; Empagliflozin; Cardiotoxicity; Doxorubicin
• ISSN: 1530-7905; 1559-0259
• DOI: 10.1007/s12012-021-09665-y

Empagliflozin (EMPA) is a SGLT-2 inhibitor that has positive effects on cardiovascular outcomes. In this study, we aim to evaluate the possible protective effects of EMPA against doxorubicin (DOX)-induced acute cardiotoxicity. Non-diabetic Sprague–Dawley rats were randomized into four groups. The control group received serum physiologic (1 ml), the EMPA group received EMPA, the DOX group was administered cumulatively 18 mg/kg body weight DOX. The DOX+EMPA group was administered DOX and EMPA. In the DOX group, LVDED (P < 0.05) and LVSED ( P  < 0.01), QTc interval ( P  < 0.001), the ratio of karyolysis and karyorrhexis ( P  < 0.001) and infiltrative cell proliferation ( P  < 0.001) were found to be higher than; EF, FS and normal cell morphology were lower than the control group ( P  < 0.001). In the DOX+EMPA group, LVEDD ( P  < 0.05) and LVESD ( P  < 0.01) values, QTc interval ( P  < 0.001), karyolysis and karyorrhexis ratios ( P  < 0.001) and infiltrative cell proliferation were lower ( P  < 0.01); normal cell morphology and EF were higher compared to the DOX group ( P  < 0.001). Our results showed that empagliflozin significantly ameliorated DOX-induced acute cardiotoxicity.