Possibilities of dapagliflozin-induced cardioprotection on doxorubicin + cyclophosphamide mode of chemotherapy-induced cardiomyopathy

Ashot Avagimyan; Mohammad Sheibani; Nana Pogosova; Lusine Mkrtchyan; Hasmik Yeranosyan; Anahit Aznauryan; Karmen Sahaakyan; Federica Fogacci; Arrigo Cicero; Davood Shafie; Nizal Sarrafzadegan

doi:10.1016/j.ijcard.2023.131331

Possibilities of dapagliflozin-induced cardioprotection on doxorubicin + cyclophosphamide mode of chemotherapy-induced cardiomyopathy

Int J Cardiol. 2023 Nov 15:391:131331. doi: 10.1016/j.ijcard.2023.131331. Epub 2023 Sep 4.

Authors

Affiliations

¹ Department of Anatomical Pathology and Clinical Morphology, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia. Electronic address: dr.ashotavagimyan@gmail.com.
² Department of Pharmacology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran; Razi Drug Research Centre, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
³ National Medical Research Centre of Cardiology named after E. Chazov, Moscow, Russia.
⁴ Department of Cardiology, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia.
⁵ Department of Forensic Medicine, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia.
⁶ Department of Histology, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia.
⁷ Head of Histology Department, Yerevan State Medical University after M. Heratsi, Yerevan, Armenia.
⁸ Research Fellow, Atherosclerosis and Metabolic Disorders Research Unit, Alma Mater Studiorum University of Bologna, Bologna, Italy.
⁹ Hypertension and Cardiovascular Risk Research Unit, Alma Mater Studiorum University of Bologna, Bologna, Italy; Cardiovascular Medicine Unit, Heart, Chest and Vascular Dept., IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
¹⁰ Head of Heart Failure Centre, Isfahan Cardiovascular Research Institute, Isfahan University of Medical Science, Isfahan, Iran.
¹¹ Isfahan Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.

PMID: 37666280
DOI: 10.1016/j.ijcard.2023.131331

Abstract

Rationale: The global burden of cardiovascular (CV) and oncological diseases continues to increase. In this regard, the prevention of CV diseases (CVD) before and after cancer treatment is an urgent and unsolved problem in medicine. For this reason, our research group aimed to investigate the possibility of dapagliflozin-related cardioprotection, using an experimental model of chronic Doxorubicin (Adriamycin) + Cyclophosphamide (AC)-mode of chemotherapy-induced cardiomyopathy.

Objective: The redox balance, lipid metabolism, endothelial dysfunction, and myocardial damage parameters were measured to evaluate the pathways of dapagliflozin-induced stabilization of CV homeostasis.

Methods: For this study, 80 inbred Wistar rats were randomly assigned to four equally sized groups. A model of chronic cardiotoxicity was attained by using doxorubicin and cyclophosphamide co-administration. In the case, the markers of redox-balance, cholesterol metabolism, endothelial dysfunction, myocardial alteration, and morphological examination were assessed.

Results: For all parameters, statistically significant deviations were obtained, emphasizing the sequel of AC-mode chemotherapy-related detergent effect on CV system (group 2). Moreover, the data obtained from dapagliflozin-treated groups (group 3) showed that this strategy provide limitation of lipid peroxidation, cholesterol metabolism and endothelial function normalization, with subsequent morphological preservation of myocardium.

Conclusion: Dapagliflozin has a broad spectrum of pleiotropic influences, namely cholesterol-lowering, anti-inflammatory, and endothelium-stabilizing properties. These properties provide a favorable environment for the prevention of chemotherapy-related cardiomyopathy.

Keywords: Atherosclerosis; Cardiotoxicity; Endothelium; Myocardial metabolism.