Uzun Mehmet Hakan, Erden Aziz, Ulusan Sebahat, Özkan Emine Elif, Özseven Alper, Gülle Kanat, Şahin Adnan, Sert Selim Süleyman, Şeker Kadir, Cebeci Hüseyin Emre, Ekiz Muhammet Ali, Aydoğdu Seda, Karaibrahimoğlu Adnan, Kuyumcu Mevlüt Serdar
Department of Cardiology, Republic of Türkiye Ministry of Health, Kütahya City Hospital, Kütahya, Türkiye.
Süleyman Demirel University, Faculty of Medicine, Isparta, Türkiye.
Anatol J Cardiol. 2025 Mar 10;29(4):193-200. doi: 10.14744/AnatolJCardiol.2025.4818.
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.
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.
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).
The protective effects of DAPA against left ventricular remodeling and dysfunction in RT-induced cardiomyopathy model were observed in this study.
随着成年人群中癌症发病率的上升，放射治疗（RT）经常被用作各种癌症类型治疗的关键组成部分。由于电离辐射的特性，损伤通常发生在与原发性肿瘤定位相邻的解剖组织内。达格列净（DAPA）最初作为一种口服抗糖尿病药物开发，在DAPA-HF试验中已显示出强大的心脏保护作用。本研究调查了DAPA对放疗诱导的心脏细胞损伤的心脏保护作用。
总共获得40只雄性Wistar白化大鼠，并进行为期10天的预处理期以适应实验室环境。之后，将大鼠分为4组，每组10只（对照组 = 10只，DAPA组 = 10只，RT组 = 10只，RT + DAPA组 = 10只）。同时，RT组和RT + DAPA组在0.60 Gy/min的条件下接受单次剂量20格雷（Gy）的X射线照射4×4 cm区域，DAPA组和RT + DAPA组每天灌胃10 mg/kg的DAPA。在研究的第二周，通过超声心动图和心电图对大鼠进行检查。此外，采用组织病理学方法评估心脏毒性水平。
与RT组相比，DAPA + RT组的射血分数值降低了17.3%（P <.001）。此外，RT组的校正QT间期延长和QRS增宽分别比DAPA + RT组高11.5%和17.4%（两个值均P <.001）。虽然RT组发现有严重的肌溶解、炎性细胞浸润和坏死改变，但DAPA + RT组的肌溶解减少68%，炎性细胞浸润减少64%，坏死减少55%（所有值均P <.001）。
本研究观察到DAPA对放疗诱导的心肌病模型中的左心室重构和功能障碍具有保护作用。
