Arrhythmogenic effects and cardioprotective effects of dapagliflozin against radiotherapy induced cardiac damage

Abstract Background With increasing incidence of cancer among the adult population, radiotherapy (RT) is frequently used as a critical component in the treatment of various cancer types. Due to the nature of ionizing radiation, damage usually occurs within the tissues in anatomical neighborhood with the primary tumor localisation. Dapagliflozin (DAPA), originally developed as an oral anti-diabetic medication, has shown to have potent cardioprotective effects in the DAPA-HF trial. In this study, we aimed to investigate cardioprotective effects of Dapagliflozin against radiotherapy induced cardiac cellular damage. Methods A total of 40 male rats were obtained, and were subjected to a 10 day pretreatment period to accommodate laboratory settings. Afterwards, rats were divided into 4 groups consisting of 10 each (control = 10, dapagliflozin = 10, radiotherapy = 10, radiotherapy + dapagliflozin = 10). Meanwhile, radiotherapy and radiotherapy + dapagliflozin groups received a single dose of 20 Gray (Gy) X-ray to 4 x 4 cm area at 0.60 Gy/min, and dapagliflozin and radiotherapy + dapagliflozin groups were gavaged daily with 10 mg/kg dapagliflozin. In the second week of the study, rats were examined by echocardiography and electrocardiogram. Furthermore, histopathological method was used to evaluate the level of cardiotoxicity. Results Ejection fraction value decreased was 17.3% lower in the DAPA + RT group, compared with the RT group (p < 0.001). In addition, QTc prolongation and QRS widening were 11.5% and 17.4% more in the RT group, compared with the DAPA + RT group, respectively (p < 0.001 for both values). While the sarcomyolysis, inflammatory cell infiltration, and necrotic changes were found to be severe in the RT group, the DAPA + RT group had 68% lower sarcomyolysis, 64% lower inflammatory cell infiltration, and 55% lower necrosis (p < 0.001 for all values). Conclusions In our study, we observed the protective effects of DAPA against LV remodeling and dysfunction in RT-induced cardiomyopathy model. Cardiomyopathy, Left Ventricular Dysfunction, Radiotherapy, SGLT2 inhibitorsStudy Design