Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences, United Arab Emirates University, PO Box-17666, Al Ain 17666, United Arab Emirates.
Department of Internal Medicine, College of Medicine and Health Sciences, United Arab Emirates University, PO Box-17666, Al Ain 17666, United Arab Emirates.
J Agric Food Chem. 2021 Jul 7;69(26):7334-7343. doi: 10.1021/acs.jafc.0c05667. Epub 2021 Jun 25.
The clinical usage of doxorubicin (DOX), a potent anthracycline antineoplastic drug, is limited due to its cardiotoxicity. The aim of this study was to assess the possible cardioprotective effects of nerolidol (NERO) in a rat model of DOX-induced chronic cardiotoxicity and the underlying molecular mechanisms. DOX (2.5 mg/kg) was injected intraperitoneally once in a week for 5 weeks to induce chronic cardiotoxicity in male albino Wistar rats. The rats were treated with NERO (50 mg/kg, orally) 6 days a week for a duration of 5 weeks. DOX-injected rats showed a significant decline in cardiac function, elevated levels of serum cardiac marker enzymes, and enhanced oxidative stress markers along with altered PI3K/Akt and Nrf2/Keap1/HO-1 signaling pathways. DOX also triggered the activation of NF-κB/MAPK signaling and increased the levels/expression of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) and expression of inflammatory mediators (iNOS and COX-2) in the heart. DOX activated NLRP3 inflammasome-mediated pyroptotic cell death along with fibrosis, mitochondrial dysfunction, DNA damage, and apoptosis in the myocardium. Additionally, histological studies, TUNEL staining, and myocardial lesions revealed structural alterations of the myocardium. NERO treatment showed considerable protective effects on the biochemical and molecular parameters studied. The findings demonstrate that NERO protects against DOX-induced chronic cardiotoxicity and the observed cardioprotective effects are attributed to its potent antioxidant and free radical scavenging properties.
多柔比星（DOX）是一种有效的蒽环类抗肿瘤药物，但由于其心脏毒性，临床应用受到限制。本研究旨在评估橙花叔醇（NERO）在 DOX 诱导的慢性心脏毒性大鼠模型中的可能心脏保护作用及其潜在的分子机制。DOX（2.5mg/kg）每周腹腔注射一次，共 5 周，诱导雄性白化 Wistar 大鼠慢性心脏毒性。大鼠每周接受 NERO（50mg/kg，口服）治疗 6 天，共 5 周。DOX 注射大鼠的心脏功能明显下降，血清心脏标志物酶水平升高，氧化应激标志物增强，同时改变了 PI3K/Akt 和 Nrf2/Keap1/HO-1 信号通路。DOX 还触发了 NF-κB/MAPK 信号的激活，并增加了心脏中促炎细胞因子（TNF-α、IL-6 和 IL-1β）和炎症介质（iNOS 和 COX-2）的水平/表达。DOX 激活 NLRP3 炎性小体介导的细胞焦亡以及纤维化、线粒体功能障碍、DNA 损伤和心肌细胞凋亡。此外，组织学研究、TUNEL 染色和心肌损伤显示心肌的结构改变。NERO 治疗对研究的生化和分子参数显示出显著的保护作用。研究结果表明，NERO 可预防 DOX 诱导的慢性心脏毒性，观察到的心脏保护作用归因于其强大的抗氧化和自由基清除特性。
Zotero 插件