Abstract
BackgroundDoxorubicin (DOX) is one of the most potent antitumor agents available; however, its clinical use is limited because of the risk of severe cardiotoxicity. Though numerous studies have ascribed DOX cardiomyopathy to specific cellular pathways, the precise mechanism remains obscure. Sini decoction (SND) is a well-known formula of Traditional Chinese Medicine (TCM) and is considered as efficient agents against DOX-induced cardiomyopathy. However, its action mechanisms are not well known due to its complex components.Methodology/Principal FindingsA tissue-targeted metabonomic method using gas chromatography–mass spectrometry was developed to characterize the metabolic profile of DOX-induced cardiomyopathy in mice. With Elastic Net for classification and selection of biomarkers, twenty-four metabolites corresponding to DOX-induced cardiomyopathy were screened out, primarily involving glycolysis, lipid metabolism, citrate cycle, and some amino acids metabolism. With these altered metabolic pathways as possible drug targets, we systematically analyzed the protective effect of TCM SND, which showed that SND administration could provide satisfactory effect on DOX-induced cardiomyopathy through partially regulating the perturbed metabolic pathways.Conclusions/SignificanceThe results of the present study not only gave rise to a systematic view of the development of DOX-induced cardiomyopathy but also provided the theoretical basis to prevent or modify expected damage.
Highlights
Doxorubicin (DOX) is a powerful anticancer antibiotic [1]
The present study demonstrates, for the first time, a GC-MSbased metabonomic analysis of DOX-induced cardiomyopathy in mice, identifying 24 potential biomarkers relevant to the disturbance of myocardial energy metabolism primarily involving glycolysis, lipid metabolism, citrate cycle, and some amino acids metabolism
It was confirmed that Chinese Medicine Sini decoction (SND) could play its role in DOX-induced cardiomyopathy by intervening in some metabolic pathways, such as glycolysis, lipid metabolism, citrate cycle, and some amino acids metabolism, which might be mapped by restoring alterations in some biomarkers found in this research
Summary
Doxorubicin (DOX) is a powerful anticancer antibiotic [1]. The clinical use of DOX is often limited because of its undesirable serious cardiotoxic side effects, which frequently lead to congestive heart failure [2,3,4]. Sini decoction (SND), which is officially recorded in the Chinese Pharmacopoeia 2010 edition and has been used to prevent or treat cardiovascular disease as well as DOX-induced cardiomyopathy for many years [17,18,19,20], is a representative TCM. It is composed of three medicinal plants: Acontium carmichaeli, Glycyrrhiza uralensis and Zingiber officinale. Sini decoction (SND) is a well-known formula of Traditional Chinese Medicine (TCM) and is considered as efficient agents against DOX-induced cardiomyopathy. Its action mechanisms are not well known due to its complex components
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