Protective effect of Lycium barbarum on doxorubicin-induced cardiotoxicity.
The objective of this work was to explore the hypothesis that Lycium barbarum (LB) may be protective against doxorubicin (DOX)-induced cardiotoxicity through antioxidant-mediated mechanisms. Male SD rats were treated with distilled water or a water extract of LB (25 mg/kg, p.o.) daily and saline or DOX (5 mg/kg, i.v.) weekly for 3 weeks. Mortality, general condition and body weight were observed during the experiment. DOX-induced cardiotoxicity was assessed by electrocardiograph, heart antioxidant activity, serum levels of creatine kinase (CK) and aspartate aminotransferase (AST) and histopathological change. The DOX group showed higher mortality (38%) and worse physical characterization. Moreover, DOX caused myocardial injury manifested by arrhythmias and conduction abnormalities in ECG (increased QT and ST intervals and ST elevation), a decrease of heart antioxidant activity, an increase of serum CK and AST, as well as myocardial lesions. Pretreatment with LB significantly prevented the loss of myofibrils and improved the heart function of the DOX-treated rats as evidenced from lower mortality (13%), normalization of antioxidative activity and serum AST and CK, as well as improving arrhythmias and conduction abnormalities. These results suggested that LB elicited a typical cardioprotective effect on DOX-related oxidative stress. Furthermore, in vitro cytotoxic study showed the antitumor activity of DOX was not compromised by LB. It is possible that LB could be used as a useful adjunct in combination with DOX chemotherapy.
Xin
Yan-Fei
YF
State Key Laboratory of Safety Evaluation for New Drug, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China.
Zhou
Guo-Liang
GL
Deng
Zu-Yue
ZY
Chen
Yun-Xiang
YX
Wu
Yue-Guo
YG
Xu
Pan-Sheng
PS
Xuan
Yao-Xian
YX
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood*; D002277:Carcinoma / Q000188:drug therapy; D045744:Cell Line, Tumor; D003402:Creatine Kinase / Q000097:blood*; D004317:Doxorubicin / Q000009:adverse effects; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D032305:Lycium; D008297:Male; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000975:Antioxidants; D010936:Plant Extracts; D004317:Doxorubicin; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase