Comparison of Cardioprotective Effects of Dapagliflozin and Trimetazidine in the Model of Doxorubicin-Cyclophosphamide Cardiotoxicity

Abstract

Background: Data published by task groups of the Ministry of Health of the Russian Federation, the European Society of Cardiology, and other medical associations and institutions show that chemotherapy-induced cardiomyopathy is still a challenging issue that requires further research.Objective: To compare the cardioprotective potential of trimetazidine and dapagliflozin in a rat model of doxorubicin-cyclophospha-mide cardiomyopathy.Materials and methods: Our randomized in vivo experimental study included 80 Wistar female rats. Doxorubicin and cyclophosphamide were administered at a dose of 15 mg/kg and 150 mg/kg, respectively. Trimetazidine (42 mg/kg) and dapagliflozin (14 mg/kg) were additionally administered to groups 3 and 4, respectively. The total duration of the experiment was 14 days.Results: Doxorubicin+cyclophosphamide mode of chemotherapy induces the development of toxic-ischemic cardiomyopathy. The trimetazidine and dapagliflozin administration was accompanied by stabilization of cardiovascular parameters. Comparison of both drugs’ cardioprotective properties revealed a clear advantage of dapagliflozin over trimetazidine, especially in terms of such an important indicator as N-terminal pro-B-type natriuretic peptide.Conclusions: Further research aimed at exploring the cardioprotective potential of dapagliflozin against cardiovascular complications of chemotherapy is justified from a pathogenetic point of view.

Keywords

• cardiotoxicity
• dapagliflozin
• trimetazidine
• oxidative stress