Xiong Chen, Wu Yan-Zhao, Zhang Yu, Wu Zi-Xiao, Chen Xue-Yan, Jiang Ping, Guo Hui-Cai, Xie Ke-Rang, Wang Ke-Xin, Su Su-Wen
Key Laboratory of Neural and Vascular Biology, Ministry of Education, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
Key Laboratory of Pharmacology and Toxicology for New Drugs, Department of Pharmacology, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China.
Oncol Lett. 2018 Apr;15(4):5721-5729. doi: 10.3892/ol.2018.8020. Epub 2018 Feb 9.
Doxorubicin (DOX) is a potent and broad-spectrum anthracycline chemotherapeutic agent, but dose-dependent cardiotoxic side effects limit its clinical application. This toxicity is closely associated with the generation of reactive oxygen species (ROS) radical during DOX metabolism. The present study investigated the effects of Berberine (Ber) on DOX-induced acute cardiac injury in a rat model and analysed its mechanism in cardiomyocytes . Serum creatine kinase (CK), creatine kinase isoenzyme (CK-MB) and malondialdehyde (MDA) levels were significantly increased in the DOX group compared with the control group. This increase was accompanied by cardiac histopathological injury and a decrease in cardiomyocyte superoxide dismutase (SOD) and catalase (CAT). CK, CK-MB and MDA levels decreased and SOD and CAT levels increased in the Ber-treated group compared to the DOX group. Ber ameliorated the DOX-induced increase in cytosolic calcium concentration ([Ca]), attenuated mitochondrial Ca overload and restored the DOX-induced loss of mitochondrial membrane potential . These results demonstrated that Ber exhibited protective effects against DOX-induced heart tissue free radical injury, potentially via the inhibition of intracellular Ca elevation and attenuation of mitochondrial dysfunction.
阿霉素(DOX)是一种强效的广谱蒽环类化疗药物,但剂量依赖性心脏毒性副作用限制了其临床应用。这种毒性与DOX代谢过程中活性氧(ROS)自由基的产生密切相关。本研究调查了黄连素(Ber)对大鼠模型中DOX诱导的急性心脏损伤的影响,并分析了其在心肌细胞中的作用机制。与对照组相比,DOX组血清肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)和丙二醛(MDA)水平显著升高。这种升高伴随着心脏组织病理学损伤以及心肌细胞超氧化物歧化酶(SOD)和过氧化氢酶(CAT)的降低。与DOX组相比,Ber治疗组的CK、CK-MB和MDA水平降低,SOD和CAT水平升高。Ber改善了DOX诱导的胞质钙浓度([Ca])升高,减轻了线粒体钙超载,并恢复了DOX诱导的线粒体膜电位丧失。这些结果表明,Ber对DOX诱导的心脏组织自由基损伤具有保护作用,可能是通过抑制细胞内钙升高和减轻线粒体功能障碍来实现的。