Electrocardiographic and biochemical evidence for the cardioprotective effect of antioxidants in acute doxorubicin-induced cardiotoxicity in the beagle dogs.
Electrocardiographic and biochemical evidence for the cardioprotective effect of antioxidants in acute doxorubicin-induced cardiotoxicity in the beagle dogs.
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DOI：
10.1248/bpb.34.1523
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发表时间：
2011-10
影响因子：
2
通讯作者：
Y. Xin;Sheng Zhang;Liqiang Gu;Shu-peng Liu;Hai-yan Gao;Z. You;Guoliang Zhou;Lei Wen;Jian Yu-Jia
中科院分区：
文献类型：
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作者：
Y. Xin;Sheng Zhang;Liqiang Gu;Shu-peng Liu;Hai-yan Gao;Z. You;Guoliang Zhou;Lei Wen;Jian Yu-Jia
多柔比星（DOX）是一种有效的抗肿瘤药物，但其活性氧介导的心脏毒性限制了其临床应用。本研究旨在探讨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DOX诱导的Beagle犬急性心脏毒性的保护作用的心电图和生化证据。在该研究中，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.））7 d后静脉注射DOX（1.5 mg/kg）。DOX（15 mg/kg）在犬中显著诱导急性心脏毒性，其特征在于传导异常（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）和天冬氨酸转氨酶（AST）升高。LBP或EDA预处理可有效缓解DOX相关的传导异常，并升高血清CK和AST。此外，生理和血清生化证据表明，EDA比LBP更有效地减轻DOX在心脏中产生的这些异常。所有这些结果证实并扩展了先前在大鼠中关于LBP或EDA对DOX诱导的心肌病的有效性的观察。
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.