Uzun Mehmet Hakan, Ulusan Sebahat, Yönet Afragül, Şeker Kadir, Sevimli Murat, Gülle Kanat, Karaibrahimoğlu Adnan, Kuyumcu Aliye, Kanat Selçuk, Alagöz Mehmet, Kuyumcu Mevlüt Serdar
Department of Cardiology, Republic of Türkiye Ministry of Health Kutahya City Hospital, Kutahya, Türkiye.
Department of Histology and Embryology, Suleyman Demirel University Health Sciences Institution, Isparta, Türkiye.
Front Cardiovasc Med. 2025 Jul 18;12:1633420. doi: 10.3389/fcvm.2025.1633420. eCollection 2025.
5-Fluorouracil (5-FU) has potential cardiotoxic effects, including direct cardiomyocyte damage, arrhythmia development, and coronary vasospasm. Numerous studies have demonstrated that dapagliflozin (DAPA) possesses cardioprotective properties. Theoretically, DAPA may have the potential to mitigate 5-FU-induced cardiotoxicity.
32 male Wistar albino rats were randomly divided into four groups of eight animals each: Control, DAPA, 5-FU, and 5-FU + DAPA. The 5-FU groups received a single intraperitoneal dose of 150 mg/kg 5-FU at the beginning of the study, while the DAPA groups were administered 10 mg/kg DAPA daily via oral gavage. Echocardiography, electrocardiography, and weight measurements were performed at baseline, and at the end of the first and second weeks. The experiment was concluded at the end of the second week, and tissue samples were collected for histopathological analysis.
Compared to the 5-FU group, the 5-FU + DAPA group exhibited a 9.5% smaller reduction in ejection fraction, a 50% lower incidence of ST-segment elevation, and a 14.16% smaller increase in heart rate. Moreover, the prolongation of PR, QTc, and QRS durations was attenuated by 8.27%, 9.91%, and 34.5%, respectively ( < 0.05 for all). Histopathological analysis also revealed significantly reduced inflammation in the 5-FU + DAPA group ( < 0.05).
Dapagliflozin has shown to have cardioprotective effects against acute cardiotoxicity in a 5-FU-induced cardiomyopathy rat model.
5-氟尿嘧啶（5-FU）具有潜在的心脏毒性作用，包括直接的心肌细胞损伤、心律失常的发生以及冠状动脉痉挛。大量研究表明，达格列净（DAPA）具有心脏保护特性。从理论上讲，达格列净可能有减轻5-FU诱导的心脏毒性的潜力。
32只雄性Wistar白化大鼠被随机分为四组，每组8只动物：对照组、达格列净组、5-FU组和5-FU + 达格列净组。在研究开始时，5-FU组接受单次腹腔注射150 mg/kg的5-FU，而达格列净组每天通过灌胃给予10 mg/kg的达格列净。在基线、第一周和第二周结束时进行超声心动图、心电图和体重测量。实验在第二周结束时结束，并收集组织样本进行组织病理学分析。
与5-FU组相比，5-FU + 达格列净组的射血分数降低幅度小9.5%，ST段抬高的发生率低50%，心率增加幅度小14.16%。此外，PR、QTc和QRS间期的延长分别减少了8.27%、9.91%和34.5%（所有P < 0.05）。组织病理学分析还显示，5-FU + 达格列净组的炎症明显减轻（P < 0.05）。
在5-FU诱导的心肌病大鼠模型中，达格列净已显示出对急性心脏毒性具有心脏保护作用。
