Faculty of Medicine, Isparta Süleyman Demirel University, Isparta, Turkey.
Department of Histology and Embryology, Faculty of Medicine, Isparta Süleyman Demirel University, Isparta, Turkey.
Anatol J Cardiol. 2023 Jun;27(6):339-347. doi: 10.14744/AnatolJCardiol.2023.2825.
Doxorubicin is a widely used agent in the treatment of cancer, but the cardiotoxicity associated with this drug limits its potential for use. The cardioprotective effects of dapagliflozin, an antidiabetic drug, have the potential to counteract the cardiotoxic effect of doxorubicin therapy. In our study, we aimed to investigate the protective effect of dapagliflozin from possible doxorubicin-induced cardiotoxicity.
A total of 40 male Wistar albino rats were divided into 4 groups consisting of 10 each (control = 10, dapagliflozin = 10, doxorubicin = 10, doxorubicin + dapagliflozin = 10). Meanwhile, doxorubicin and doxorubicin + dapagliflozin groups received a total dose of 15 mg/kg doxorubicin intraperitoneally, dapagliflozin and doxorubicin + dapagliflozin groups were gavaged daily with 10 mg/kg dapagliflozin. At the sixth week of the study, rats were examined by echocardiography and electrocardiogram. Furthermore, histopathological method was used to evaluate the level of cardiotoxicity.
Ejection fraction decreased by 15% in the doxorubicin group, and this reduction in ejection fraction was alleviated in the doxorubicin + dapagliflozin group. In addition, a 65% increase in QRS duration was observed in the group given doxorubicin, while an increase of 7% was observed in doxorubicin + dapagliflozin group. Corrected QT duration increased by 12% in the doxorubicin group, compared to 2% in doxorubicin + dapagliflozin group. Meanwhile, sarco-myolysis, inflammatory cell infiltration, and necrotic changes were examined heavily in doxorubicin group, they were minimal in doxorubicin + dapagliflozin group.
Our study showed that dapagliflozin has the potential to reduce the effects of doxorubicin-induced cardiotoxicity.
多柔比星是一种广泛用于癌症治疗的药物，但该药物的心脏毒性限制了其应用潜力。抗糖尿病药物达格列净具有心脏保护作用，有可能抵消多柔比星治疗的心脏毒性作用。在我们的研究中，我们旨在研究达格列净对可能由多柔比星引起的心脏毒性的保护作用。
将 40 只雄性 Wistar 白化大鼠分为 4 组，每组 10 只（对照组=10，达格列净组=10，多柔比星组=10，多柔比星+达格列净组=10）。同时，多柔比星和多柔比星+达格列净组腹腔内给予总剂量 15mg/kg 的多柔比星，达格列净和多柔比星+达格列净组每天灌胃给予 10mg/kg 的达格列净。在研究的第六周，通过超声心动图和心电图检查大鼠。此外，采用组织病理学方法评估心脏毒性程度。
多柔比星组的射血分数降低了 15%，而多柔比星+达格列净组的射血分数降低得到了缓解。此外，多柔比星组的 QRS 持续时间增加了 65%，而多柔比星+达格列净组增加了 7%。多柔比星组的校正 QT 持续时间增加了 12%，而多柔比星+达格列净组增加了 2%。同时，多柔比星组的肌溶解、炎症细胞浸润和坏死性改变明显，而多柔比星+达格列净组则很少。
我们的研究表明，达格列净有可能减轻多柔比星引起的心脏毒性作用。
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