State Key Laboratory of Safety Evaluation for New Drugs, Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, China.
Biol Pharm Bull. 2011;34(10):1523-6. doi: 10.1248/bpb.34.1523.
Doxorubicin (DOX) is a potent antitumor agent, but the cardiotoxicity mediated by the formation of reactive oxygen species limit its clinical use. The present study aims to explore electrocardiographic and biochemical evidence for the cardioprotective effect of two antioxidants, Lycium barbarum polysaccharides (LBP, the main antioxidant in Lycium barbarum) and edaravone (a potent free radical scavenger, EDA) against DOX-induced acute cardiotoxicity in beagle dogs. In this study, male beagle dogs received daily treatment of either LBP (20 mg/kg, per os (p.o.)) or EDA (2 mg/kg, intravenously (i.v.)) for 7 d and then followed by an intravenous injection of DOX (1.5 mg/kg). DOX (15 mg/kg) significantly induced acute cardiotoxicity in dogs characterized by conduction abnormalities (including decreased heart rate, ST segment elevation, QT intervals prolongation, inverted T wave, arrhythmia, and myocardial ischemia) and increased serum creatine kinase (CK) and aspartate aminotransferase (AST). Pretreatment with LBP or EDA effectively alleviated both DOX-associated conduction abnormalities and increased serum CK and AST. Moreover, physiological and serum biochemical evidences demonstrated that EDA is more effective than LBP in alleviating these abnormalities produced by DOX in heart. All these results confirm and extend previous observations in rats concerning the effectiveness of LBP or EDA against DOX-induced cardiomyopathy.
阿霉素（DOX）是一种有效的抗肿瘤药物，但由于其形成活性氧引起的心脏毒性限制了其临床应用。本研究旨在探讨心电图和生化证据，以证明两种抗氧化剂枸杞多糖（LBP，枸杞中的主要抗氧化剂）和依达拉奉（一种有效的自由基清除剂，EDA）对犬 DOX 诱导的急性心肌毒性的心脏保护作用。在这项研究中，雄性比格犬每天接受 LBP（20 mg/kg，口服（p.o.））或 EDA（2 mg/kg，静脉内（i.v.））治疗 7 天，然后静脉注射 DOX（1.5 mg/kg）。DOX（15 mg/kg）显著诱导犬急性心肌毒性，表现为传导异常（包括心率降低、ST 段抬高、QT 间期延长、T 波倒置、心律失常和心肌缺血）和血清肌酸激酶（CK）和天冬氨酸氨基转移酶（AST）升高。LBP 或 EDA 预处理可有效缓解 DOX 引起的传导异常和血清 CK、AST 升高。此外，生理和血清生化证据表明，EDA 比 LBP 更有效地缓解 DOX 在心脏中引起的这些异常。所有这些结果证实并扩展了先前在大鼠中关于 LBP 或 EDA 对抗 DOX 诱导的心肌病的有效性的观察结果。
