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A metabolomic study of rats with doxorubicin-induced cardiomyopathy and Shengmai injection treatment.

Chen Y, Tang Y, Zhang YC, Huang XH, Xie YQ, Xiang Y - PLoS ONE (2015)

Bottom Line: As a result of its multi-component and multi-target nature and comprehensive regulation, the pharmacological mechanisms underlying SMI's effects remain obscure.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.

View Article: PubMed Central - PubMed

Affiliation: The Division of Cardiology, Xin Hua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

The serum concentrations of the cardiac biomarkers across all groups.Compared with the control group, *p<0.05; compared with the DOX group, #p<0.01.
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pone.0125209.g002: The serum concentrations of the cardiac biomarkers across all groups.Compared with the control group, *p<0.05; compared with the DOX group, #p<0.01.

Mentions: The serum concentrations of the cardiac biomarkers are included in Fig 2. A biomarker of congestive heart failure, the serum BNP concentration in the DOX group was significantly higher compared with the other groups at the end of eight weeks (p<0.01). The serum BNP concentration in the DOX + SMI group was significantly lower compared with the DOX group (p<0.01). The serum concentrations of cTNI, myoglobin and CK-MB of the DOX group were significantly higher than those of the control group (p<0.05), whereas the concentrations of the DOX + SMI group were significantly lower than those of the DOX group, with the exception of myoglobin (p<0.01). The myoglobin concentration of the DOX + SMI group was mildly lower than that of the DOX group (p = 0.07).


A metabolomic study of rats with doxorubicin-induced cardiomyopathy and Shengmai injection treatment.

Chen Y, Tang Y, Zhang YC, Huang XH, Xie YQ, Xiang Y - PLoS ONE (2015)

The serum concentrations of the cardiac biomarkers across all groups.Compared with the control group, *p<0.05; compared with the DOX group, #p<0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4418690&req=5

pone.0125209.g002: The serum concentrations of the cardiac biomarkers across all groups.Compared with the control group, *p<0.05; compared with the DOX group, #p<0.01.
Mentions: The serum concentrations of the cardiac biomarkers are included in Fig 2. A biomarker of congestive heart failure, the serum BNP concentration in the DOX group was significantly higher compared with the other groups at the end of eight weeks (p<0.01). The serum BNP concentration in the DOX + SMI group was significantly lower compared with the DOX group (p<0.01). The serum concentrations of cTNI, myoglobin and CK-MB of the DOX group were significantly higher than those of the control group (p<0.05), whereas the concentrations of the DOX + SMI group were significantly lower than those of the DOX group, with the exception of myoglobin (p<0.01). The myoglobin concentration of the DOX + SMI group was mildly lower than that of the DOX group (p = 0.07).

Bottom Line: As a result of its multi-component and multi-target nature and comprehensive regulation, the pharmacological mechanisms underlying SMI's effects remain obscure.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.

View Article: PubMed Central - PubMed

Affiliation: The Division of Cardiology, Xin Hua Hospital, Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus