Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
PLoS One. 2013 May 28;8(5):e64526. doi: 10.1371/journal.pone.0064526. Print 2013.
Doxorubicin (Dox) is an anthracycline antibiotic for cancer therapy with limited usage due to cardiotoxicity. Isorhamnetin is a nature antioxidant with obvious cardiac protective effect. The aim of this study is going to investigate the possible protective effect of isorhamnetin against Dox-induced cardiotoxicity and its underlying mechanisms. In an in vivo investigation, rats were intraperitoneally (i.p.) administered with Dox to duplicate the model of Dox-induced chronic cardiotoxicity. Daily pretreatment with isorhamnetin (5 mg/kg, i.p.) for 7 days was found to reduce Dox-induced myocardial damage significantly, including the decline of cardiac index, decrease in the release of serum cardiac enzymes and amelioration of heart vacuolation. In vitro studies on H9c2 cardiomyocytes, isorhamnetin was effective to reduce Dox-induced cell toxicity. A further mechanism study indicated that isorhamnetin pretreatment can counteract Dox-induced oxidative stress and suppress the activation of mitochondrion apoptotic pathway and mitogen-activated protein kinase pathway. Isorhamnetin also potentiated the anti-cancer activity of Dox in MCF-7, HepG2 and Hep2 cells. These findings indicated that isorhamnetin can be used as an adjuvant therapy for the long-term clinical use of Dox.
多柔比星（Dox）是一种用于癌症治疗的蒽环类抗生素，由于其心脏毒性，其应用受到限制。山奈酚是一种具有明显心脏保护作用的天然抗氧化剂。本研究旨在探讨山奈酚对多柔比星诱导的心脏毒性的可能保护作用及其潜在机制。在体内研究中，大鼠通过腹腔内（i.p.）给予多柔比星来复制多柔比星诱导的慢性心脏毒性模型。研究发现，山奈酚（5mg/kg，i.p.）每天预处理 7 天可显著减轻多柔比星诱导的心肌损伤，包括心指数下降、血清心脏酶释放减少和心脏空泡化改善。在 H9c2 心肌细胞的体外研究中，山奈酚可有效减轻多柔比星诱导的细胞毒性。进一步的机制研究表明，山奈酚预处理可以拮抗多柔比星诱导的氧化应激，并抑制线粒体凋亡途径和丝裂原激活蛋白激酶途径的激活。山奈酚还增强了多柔比星在 MCF-7、HepG2 和 Hep2 细胞中的抗癌活性。这些发现表明，山奈酚可作为多柔比星长期临床应用的辅助治疗药物。
