Cardioprotective effects of dapagliflozin against the acute cardiotoxic effects of 5-fluorouracil
Background5-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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2025.1633420/full |
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| author | Mehmet Hakan Uzun Sebahat Ulusan Afragül Yönet Kadir Şeker Murat Sevimli Kanat Gülle Adnan Karaibrahimoğlu Aliye Kuyumcu Selçuk Kanat Mehmet Alagöz Mevlüt Serdar Kuyumcu |
| author_facet | Mehmet Hakan Uzun Sebahat Ulusan Afragül Yönet Kadir Şeker Murat Sevimli Kanat Gülle Adnan Karaibrahimoğlu Aliye Kuyumcu Selçuk Kanat Mehmet Alagöz Mevlüt Serdar Kuyumcu |
| author_sort | Mehmet Hakan Uzun |
| collection | DOAJ |
| description | Background5-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.Methods32 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.ResultsCompared 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).ConclusionsDapagliflozin has shown to have cardioprotective effects against acute cardiotoxicity in a 5-FU-induced cardiomyopathy rat model. |
| format | Article |
| id | doaj-art-55b6485fcebb4078ad7cbe53f55dd80a |
| institution | Kabale University |
| issn | 2297-055X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj-art-55b6485fcebb4078ad7cbe53f55dd80a2025-08-20T03:28:01ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2025-07-011210.3389/fcvm.2025.16334201633420Cardioprotective effects of dapagliflozin against the acute cardiotoxic effects of 5-fluorouracilMehmet Hakan Uzun0Sebahat Ulusan1Afragül Yönet2Kadir Şeker3Murat Sevimli4Kanat Gülle5Adnan Karaibrahimoğlu6Aliye Kuyumcu7Selçuk Kanat8Mehmet Alagöz9Mevlüt Serdar Kuyumcu10Department of Cardiology, Republic of Türkiye Ministry of Health Kutahya City Hospital, Kutahya, TürkiyeDepartment of Histology and Embryology, Suleyman Demirel University Health Sciences Institution, Isparta, TürkiyeDepartment of Histology and Embryology, Suleyman Demirel University Faculty of Medicine, Isparta, TürkiyeDepartment of Cardiology, Suleyman Demirel University Faculty of Medicine, Isparta, TürkiyeDepartment of Histology and Embryology, Eskisehir Osmangazi University Faculty of Medicine, Eskisehir, TürkiyeDepartment of Histology and Embryology, Suleyman Demirel University Faculty of Medicine, Isparta, TürkiyeDepartment of Biostatistics and Medical Informatics, Suleyman Demirel University Faculty of Medicine, Isparta, TürkiyeDepartment of Nutrition and Dietetics, Suleyman Demirel University Faculty of Health Sciences, Isparta, TürkiyeCardiology and Cardiac Electrophysiology, Private Clinic, Bursa, TürkiyeDepartment of Surgery, Nassau University Medical Center, East Meadow, NY, United StatesDepartment of Cardiology, Suleyman Demirel University Faculty of Medicine, Isparta, TürkiyeBackground5-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.Methods32 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.ResultsCompared 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).ConclusionsDapagliflozin has shown to have cardioprotective effects against acute cardiotoxicity in a 5-FU-induced cardiomyopathy rat model.https://www.frontiersin.org/articles/10.3389/fcvm.2025.1633420/full5-fluorouracilcardiotoxicityheart failureSGLT2 inhibitorscardiomyopathy |
| spellingShingle | Mehmet Hakan Uzun Sebahat Ulusan Afragül Yönet Kadir Şeker Murat Sevimli Kanat Gülle Adnan Karaibrahimoğlu Aliye Kuyumcu Selçuk Kanat Mehmet Alagöz Mevlüt Serdar Kuyumcu Cardioprotective effects of dapagliflozin against the acute cardiotoxic effects of 5-fluorouracil Frontiers in Cardiovascular Medicine 5-fluorouracil cardiotoxicity heart failure SGLT2 inhibitors cardiomyopathy |
| title | Cardioprotective effects of dapagliflozin against the acute cardiotoxic effects of 5-fluorouracil |
| title_full | Cardioprotective effects of dapagliflozin against the acute cardiotoxic effects of 5-fluorouracil |
| title_fullStr | Cardioprotective effects of dapagliflozin against the acute cardiotoxic effects of 5-fluorouracil |
| title_full_unstemmed | Cardioprotective effects of dapagliflozin against the acute cardiotoxic effects of 5-fluorouracil |
| title_short | Cardioprotective effects of dapagliflozin against the acute cardiotoxic effects of 5-fluorouracil |
| title_sort | cardioprotective effects of dapagliflozin against the acute cardiotoxic effects of 5 fluorouracil |
| topic | 5-fluorouracil cardiotoxicity heart failure SGLT2 inhibitors cardiomyopathy |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2025.1633420/full |
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