Cardioprotective Effects of Dapagliflozin Against Radiotherapy Induced Cardiac Damage.

Abstract

Background: With the 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 localization. Dapagliflozin (DAPA), originally developed as an oral anti-diabetic medication, has been shown to have potent cardioprotective effects in the DAPA-HF trial. The cardioprotective effects of DAPA against RT induced cardiac cellular damage were investigated in this study.

Methods: A total of 40 male Wistar albino rats were obtained and were subjected to a 10-day pretreatment period to accommodate laboratory settings. Afterwards, the rats were divided into 4 groups consisting of 10 each (control = 10, DAPA = 10, RT = 10, RT + DAPA = 10). Meanwhile, the RT and RT + DAPA groups received a single dose of 20 Gray (Gy) x-ray to 4 × 4 cm area at 0.60 Gy/min, and DAPA and RT + DAPA groups were gavaged daily with 10 mg/kg DAPA. 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: The ejection fraction value decreased by 17.3% lower in the DAPA + RT group compared with the RT group (P < .001). In addition, corrected QT interval prolongation and QRS widening were 11.5% and 17.4% higher in the RT group compared with the DAPA + RT group, respectively (P < .001 for both values). While sarcomyolysis, inflammatory cell infiltration, and necrotic changes were found to be severe in the RT group, the DAPA + RT group had 68% less sarcomyolysis, 64% less inflammatory cell infiltration, and 55% less necrosis (P < .001 for all values).

Conclusions: The protective effects of DAPA against left ventricular remodeling and dysfunction in RT-induced cardiomyopathy model were observed in this study.