Karakuyu Nasif Fatih, Savran Mehtap, Candan Ibrahim Aydin, Buyukbayram Halil Ibrahim, Erzurumlu Yalcin
Department of Pharmacology, Faculty of Pharmacy, Suleyman Demirel University, Isparta, Turkey.
Department of Pharmacology, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey.
Naunyn Schmiedebergs Arch Pharmacol. 2023 Dec;396(12):3635-3645. doi: 10.1007/s00210-023-02566-7. Epub 2023 Jun 7.
Although doxorubicin (DOX) is an effective anti-neoplastic drug for many types of cancer, particularly dose-related cardiotoxicity limits the use of the drug. In this study, it was aimed to investigate the protective effect of lercanidipine (LRD) against DOX-induced cardiotoxicity. In our study, 40 Wistar albino female rats were randomly divided into 5 groups as control, DOX, LRD 0.5 (DOX + 0.5 mg/kg LRD), LRD 1 (DOX + 1 mg/kg LRD), and LRD 2 (DOX + 2 mg/kg LRD). At the end of the experiment, the rats were sacrificed, and their blood, heart, and endothelial tissues were examined biochemically, histopathologically, immunohistochemically, and genetically. According to our findings, necrosis, tumor necrosis factor alpha activity, vascular endothelial growth factor activity, and oxidative stress were increased in the heart tissues of the DOX group. In addition, DOX treatment caused the deteriorations in biochemical parameters, and levels of autophagy-related proteins, Atg5, Beclin1, and LC3-I/II were detected. Significant dose-related improvements in these findings were observed with LRD treatment. Besides, Atg5, LC3-I/II, and Beclin1 levels evaluated by western blot revealed that LRD exerts a tissue protective effect by regulating autophagy in endothelial tissue. LRD treatment, which is a new-generation calcium channel blocker, showed antioxidant, anti-inflammatory, and anti-apoptotic properties in heart and endothelial tissue in a dose-dependent manner and also showed protective activity by regulating autophagy in endothelial tissue. With studies evaluating these mechanisms in more detail, the protective effects of LRD will be revealed more clearly.
尽管阿霉素（DOX）是一种对多种癌症有效的抗肿瘤药物，但特别是与剂量相关的心脏毒性限制了该药物的使用。在本研究中，旨在探讨乐卡地平（LRD）对DOX诱导的心脏毒性的保护作用。在我们的研究中，40只Wistar白化雌性大鼠被随机分为5组，即对照组、DOX组、LRD 0.5组（DOX + 0.5 mg/kg LRD）、LRD 1组（DOX + 1 mg/kg LRD）和LRD 2组（DOX + 2 mg/kg LRD）。实验结束时，处死大鼠，并对其血液、心脏和内皮组织进行生化、组织病理学、免疫组织化学和基因检测。根据我们的研究结果，DOX组心脏组织中的坏死、肿瘤坏死因子α活性、血管内皮生长因子活性和氧化应激增加。此外，DOX治疗导致生化参数恶化，并检测到自噬相关蛋白Atg5、Beclin1和LC3-I/II的水平。LRD治疗观察到这些结果有显著的剂量相关改善。此外，通过蛋白质印迹法评估的Atg5、LC3-I/II和Beclin1水平表明，LRD通过调节内皮组织中的自噬发挥组织保护作用。作为新一代钙通道阻滞剂的LRD治疗在心脏和内皮组织中以剂量依赖的方式表现出抗氧化、抗炎和抗凋亡特性，并且还通过调节内皮组织中的自噬表现出保护活性。随着对这些机制更详细的研究，LRD的保护作用将更清楚地显现出来。
