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

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Abstract

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.

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Acknowledgements

We thank Mustafa Kılıçkap and Meltem Tuncer for their constructive commentaries.

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This work was supported by the Turkish Cardiovascular Academy society.

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VÖB analyzed and interpreted the data and wrote manuscript, ABD and EG performed animal trial, SZ and SM performed the histological examination of the heart, AE was a major contributor in writing the manuscript. All authors read and approved the final manuscript.

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Correspondence to Veysel Özgür Barış.

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This study was conducted after its approval at the Hacettepe University Faculty of Medicine Ethics Committee’s meeting (Date: 11.11.2019, No: 2019/12) (Decision No: 2015/12-07). Experimental studies were conducted in accordance with the Declaration of Helsinki and the Guide for the Care and Use of Laboratory Animals published by the American National Health Organization. This research involves only animal participants; therefore informed consent wasn’t needed.

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Barış, V.Ö., Dinçsoy, A.B., Gedikli, E. et al. Empagliflozin Significantly Prevents the Doxorubicin-induced Acute Cardiotoxicity via Non-antioxidant Pathways. Cardiovasc Toxicol 21, 747–758 (2021). https://doi.org/10.1007/s12012-021-09665-y

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