A metabolomic study of rats with doxorubicin-induced cardiomyopathy and Shengmai injection treatment.
Doxorubicin-induced cardiomyopathy (DOX-CM) is a severe complication of doxorubicin (DOX) chemotherapy. Characterized by cumulative and irreversible myocardial damage, its pathogenesis has not been fully elucidated. Shengmai Injection (SMI), a Traditional Chinese Medicine, may alleviate myocardial injury and improve heart function in the setting of DOX-CM. As a result of its multi-component and multi-target nature and comprehensive regulation, the pharmacological mechanisms underlying SMI's effects remain obscure. The emerging field of metabolomics provides a potential approach with which to explore the pathogenesis of DOX-CM and the benefits of SMI treatment. DOX-CM was induced in rats via intraperitoneal injections of DOX. Cardiac metabolic profiling was performed via gas chromatography/mass spectrometry and ultra-performance liquid chromatography/tandem mass spectrometry. A bioinformatics analysis was conducted via Ingenuity Pathway Analysis (IPA). Eight weeks following DOX treatment, significant cardiac remodeling, dysfunction and metabolic perturbations were observed in the rats with DOX-CM. The metabolic disturbances primarily involved lipids, amino acids, vitamins and energy metabolism, and may have been indicative of both an energy metabolism disorder and oxidative stress secondary to DOX chemotherapy. However, SMI improved cardiac structure and function, as well as the metabolism of the rats with DOX-CM. The metabolic alterations induced via SMI, including the promotion of glycogenolysis, glycolysis, amino acid utilization and antioxidation, suggested that SMI exerts cardioprotective effects by improving energy metabolism and attenuating oxidative stress. Moreover, the IPA revealed that important signaling molecules and enzymes interacted with the altered metabolites. These findings have provided us with new insights into the pathogenesis of DOX-CM and the effects of SMI, and suggest that the combination of metabolomic analysis and IPA may represent a promising tool with which to explore and better understand both heart disease and TCM therapy.
The Division of Cardiology, Xin Hua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Yu
Y
Chen
The Division of Cardiology, Xin Hua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Yong
Y
Tang
The Division of Cardiology, Xin Hua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Ya-Chen
YC
Zhang
The Division of Cardiology, Xin Hua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Xiao-Hong
XH
Huang
The Division of Cardiology, Xin Hua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Yu-Quan
YQ
Xie
The Division of Cardiology, Xin Hua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
Yin
Y
Xiang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000097:blood / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000188:drug therapy*; D004317:Doxorubicin / Q000009:adverse effects*; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000627:therapeutic use*; D005355:Fibrosis; D007267:Injections; D008297:Male; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D055432:Metabolomics / Q000379:methods*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D025341:Principal Component Analysis; D017207:Rats, Sprague-Dawley; D014463:Ultrasonography
D015415:Biomarkers; D004338:Drug Combinations; D004365:Drugs, Chinese Herbal; C009252:fructus schizandrae, radix ginseng, radix ophiopogonis drug combination; D004317:Doxorubicin