Sodium–glucose Cotransporter 2 Inhibitor Dapagliflozin Reduces Systemic H–fabp and Monocyte–to–lymphocyte Ratio in Preclinical Models of Antracycline Induced Cardiotoxicity

Abstract Background Anthracyclines are an effective and widely used chemotherapy agent in the treatment of multiple solid organ tumors and hematologic malignancies. The use of anthracyclines as a standard cancer therapy is limited by the potential for the development of cardiac dysfunction, arrhythmias, and clinical heart failure. Dapagliflozin exerts several cardiometabolic benefits in patients with and wthout T2DM through SGLT2–NLRP3 mediated pathways. Purpose In this study, we highlighted on new beneficial properties of Dapagliflozin in preclinical models of doxorubicin–induced cardiotoxicity. Methods Female C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n=6), DAPA at 12 mg/kg (DAPA, n=6) or doxorubicin combined to DAPA (DOXO–DAPA, n=6). After treatments, plasma levels of H–FABP and monocyte–to–lymphocyte ratio were determined through selective quantitative methods. Results Dapagliflozin associated to Doxorubicin reduces of 48,7% plasma levels of H–FABP compared to DOXO group (p0.001). Myocardial expression of H–FABP were also reduced, indicating cardioprotective properties of SGLT2i. Moreover, monocyte–to–lymphocyte ratio was strongly enhanced after DOXO therapy, indicating systemic pro–inflammatory properties; notably, Dapagliflozin reduced of 32,8% the monocyte–to–lymphocyte ratio compared to only DOXO treated mice (p0.005). Conclusion For the first time, Dapagliflozin demonstrated a significant reductions of monocyte–to–lymphocyte ratio during doxorubicin therapy, indicating new potential pathways of cardioprotection in cancer patients.