title: Electrocardiographic and biochemical evidence for the cardioprotective effect of antioxidants in acute doxorubicin-induced cardiotoxicity in the beagle dogs.
abstract: 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.
authors.affiliation: State Key Laboratory of Safety Evaluation for New Drugs, Center of Safety Evaluation, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang 310013, China. xinyanfei@gmail.com
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Xin
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.forename: Liqiang
authors.initials: L
authors.lastname: Gu
authors.forename: Shupeng
authors.initials: S
authors.lastname: Liu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Gao
authors.forename: Zhenqiang
authors.initials: Z
authors.lastname: You
authors.forename: Guoliang
authors.initials: G
authors.lastname: Zhou
authors.forename: Lei
authors.initials: L
authors.lastname: Wen
authors.forename: Jian
authors.initials: J
authors.lastname: Yu
authors.forename: Yaoxian
authors.initials: Y
authors.lastname: Xuan
mesh_terms: D000208:Acute Disease; D000410:Alanine Transaminase / Q000187:drug effects; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000633:toxicity; D000975:Antioxidants / Q000494:pharmacology*; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000187:drug effects; D001919:Bradycardia / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003402:Creatine Kinase / Q000187:drug effects; D004285:Dogs; D004317:Doxorubicin / Q000494:pharmacology / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D000077553:Edaravone; D004562:Electrocardiography / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006321:Heart; D006329:Heart Conduction System / Q000473:pathology; D006331:Heart Diseases / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D011897:Random Allocation
chemical_list: D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D016166:Free Radical Scavengers; C500223:lycium barbarum polysaccharide; D004317:Doxorubicin; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003402:Creatine Kinase; D000077553:Edaravone; D000983:Antipyrine