Cardioprotective effects of dapagliflozin against the acute cardiotoxic effects of 5-fluorouracil

Abstract

Background: 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. Methods: 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. Results: 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 (p < 0.05 for all). Histopathological analysis also revealed significantly reduced inflammation in the 5-FU + DAPA group (p < 0.05). Conclusions: Dapagliflozin has shown to have cardioprotective effects against acute cardiotoxicity in a 5-FU-induced cardiomyopathy rat model.