Belen E, Canbolat I P, Yigittürk G, Cetinarslan Ö, Akdeniz C S, Karaca M, Sönmez M, Erbas O
Department of Cardiology, Haseki Education and Research Hospital, Istanbul, Turkey.
Eur Rev Med Pharmacol Sci. 2022 Jun;26(12):4403-4408. doi: 10.26355/eurrev_202206_29079.
Cancer is the second most common non-communicable disease group in the world and its frequency is increasing. In parallel, side effects of drugs used in cancer treatment are frequently encountered. Doxorubicin (DOX) is one of the most effective multi-purpose anticancer drugs. However, its use is significantly limited due to the risk of cardiotoxicity. Sodium-glucose cotransporter-2 inhibitors are a group of antidiabetic drugs that have been shown to reduce cardiovascular events. Our aim is to examine the preventive effect of dapagliflozin on DOX-induced cardiac damage.
We used 30 albino rats. 20 of 30 rats were administered doxorubicin for cardiomyopathy model. The rats in the DOX arm were divided into two groups: those given penicillin and placebo. After the rats were terminated, tissues were prepared for histopathological and immunohistochemical examination. TNF-α, pro-BNP, troponin T and plasma FGF-21 levels were also measured in plasma.
The mean concentrations of cTnT and pro-BNP in the plasma of the DOX treated rats demonstrated a significantly higher value compared to the control group. Treatment with dapagliflozin caused a significant reduction in plasma cTnT, pro-BNP and TNF-α levels concentrations compared to the DOX control group (p < 0.001). The group of rats treated with dapagliflozin was effective in significantly decreasing the FGF-21 concentration and the percentage of fibronectin immunoexpression compared to the DOX control group (p < 0.0001).
This study revealed, for the first time, that dapagliflozin can improve DOX-induced cardiac dysfunction and pathological changes in non-diabetic rats. This result has shown that dapaglifozin, may be promising in terms of preventing cardiac damage that may develop in cancer treatment.
癌症是世界上第二常见的非传染性疾病组，其发病率正在上升。与此同时，癌症治疗中使用的药物的副作用也经常出现。阿霉素（DOX）是最有效的多用途抗癌药物之一。然而，由于心脏毒性风险，其使用受到显著限制。钠-葡萄糖协同转运蛋白-2抑制剂是一类已被证明可减少心血管事件的抗糖尿病药物。我们的目的是研究达格列净对阿霉素诱导的心脏损伤的预防作用。
我们使用了30只白化大鼠。30只大鼠中的20只被给予阿霉素以建立心肌病模型。阿霉素组的大鼠被分为两组：给予青霉素的大鼠和给予安慰剂的大鼠。大鼠处死后，制备组织用于组织病理学和免疫组织化学检查。还测量了血浆中的肿瘤坏死因子-α、脑钠肽前体、肌钙蛋白T和血浆成纤维细胞生长因子-21水平。
与对照组相比，阿霉素处理的大鼠血浆中的肌钙蛋白T和脑钠肽前体的平均浓度显著更高。与阿霉素对照组相比，达格列净治疗使血浆肌钙蛋白T、脑钠肽前体和肿瘤坏死因子-α水平浓度显著降低（p < 0.001）。与阿霉素对照组相比，达格列净治疗组的大鼠在显著降低成纤维细胞生长因子-21浓度和纤连蛋白免疫表达百分比方面有效（p < 0.0001）。
本研究首次揭示，达格列净可改善阿霉素诱导的非糖尿病大鼠的心脏功能障碍和病理变化。这一结果表明，达格列净在预防癌症治疗中可能发生的心脏损伤方面可能很有前景。
