Angelica sinensis: a novel adjunct to prevent doxorubicin-induced chronic cardiotoxicity.
Doxorubicin is an anthracycline antibiotic agent used in the treatment of a variety of solid and haematopoietic tumours, but its use is limited by formation of metabolites that induce acute and chronic cardiac toxicities. Angelica sinensis has been widely used to treat cardiovascular and cerebrovascular diseases in China. In the present study, we used an in vivo mouse model to explore whether A. sinensis could protect against doxorubicin-induced chronic cardiotoxicity. Male ICR mice were treated with distilled water or water extraction of A. sinensis (15 g/kg, orally) daily for 4 weeks, followed by saline or doxorubicin (15 mg/kg, intravenously) treatments weekly. Cardiotoxicity was assessed by electrocardiograph, antioxidant activity in cardiac tissues, serum levels of creatine kinase, aspartate aminotransferase (AST) and histopathological change in cardiac tissues. A cumulative dose of doxorubicin (60 mg/kg) caused animal death and myocardial injury characterized by increased QT interval and decreased heart rate in electrocardiograph, decrease of heart antioxidant activity, increase of serum AST, as well as myocardial lesions. Pre-treatment with A. sinensis significantly reduced mortality and improved heart performance of the doxorubicin-treated mice as evidenced from normalization of antioxidative activity and serum AST, preventing loss of myofibrils as well as improving arrhythmias and conduction abnormalities. Furthermore, the in vitro cytotoxic study showed that A. sinensis did not compromise the antitumour activity of doxorubicin. These results suggested that A. sinensis elicited a typical cardioprotective effect on doxorubicin-related oxidative stress, and could be a novel adjunct in the combination with doxorubicin chemotherapy.
Xin
Yan-Fei
YF
State Key Laboratory of Safety Evaluation for New Drugs, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, China.
Zhou
Guo-Liang
GL
Shen
Min
M
Chen
Yun-Xiang
YX
Liu
Shu-Peng
SP
Chen
Guo-Chan
GC
Chen
Hao
H
You
Zhen-Qiang
ZQ
Xuan
Yao-Xian
YX
D000284:Administration, Oral; D029971:Angelica sinensis / Q000737:chemistry*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity*; D000975:Antioxidants / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D002316:Cardiotonic Agents / Q000494:pharmacology; D003402:Creatine Kinase / Q000097:blood; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity*; D004347:Drug Interactions; D004562:Electrocardiography; D006331:Heart Diseases / Q000139:chemically induced / Q000401:mortality / Q000517:prevention & control*; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D009210:Myofibrils / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology*; D011897:Random Allocation
D000903:Antibiotics, Antineoplastic; D000975:Antioxidants; D002316:Cardiotonic Agents; D010936:Plant Extracts; D004317:Doxorubicin; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase