title: Myocardial lipidomics profiling delineate the toxicity of traditional Chinese medicine Aconiti Lateralis radix praeparata.
abstract: BACKGROUND
  The lateral root of Aconitum has been popularly used in traditional Chinese medicine (TMC) known as Fuzi which is beneficial for the treatment of various diseases, such as rheumatism, painful joints, syncope and bronchial asthma. However, it has a potential carditoxicity with a relatively narrow margin of safety.
  
  
  OBJECTIVE
  This paper was designed to explore the mechanisms of Fuzi's toxicity and find out potential tissue-specific biomarkers of toxic effects.
  
  
  METHODS
  A myocardial lipidomics based on ultraperformance lipid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC/Q-TOF MS) was developed to compare three cardiac lipid extraction methods and investigate the changes of lipids in mice heart of three different dosage groups. In addition, we concurrently inspected the biochemical parameters in plasma, observed the histology of the heart and recorded the electrocardiogram (ECG).
  
  
  RESULTS
  The cardiotoxicity of Fuzi was dose-dependent, and the high-dose group obviously manifested the heart damage in histology and a certain degree of arrhythmia. Significant changes of 14 lipid metabolites which primarily involved in phospholipid metabolism, sphingolipid metabolism, saturated fatty acid oxidation and unsaturated fatty acid peroxidation were identified and considered as the potential biomarkers of Fuzi toxicity.
  
  
  CONCLUSIONS
  The lipidomics approach is helpful to search potential tissue-specific biomarkers and understand the underlying mechanisms of Fuzi toxicity on the heart.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai 200433, PR China.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Cai
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
authors.forename: Guangguo
authors.initials: G
authors.lastname: Tan
authors.forename: Si
authors.initials: S
authors.lastname: Wu
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.forename: Ziyang
authors.initials: Z
authors.lastname: Lou
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Chai
mesh_terms: D031841:Aconitum; D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D004365:Drugs, Chinese Herbal / Q000633:toxicity*; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D050356:Lipid Metabolism / Q000187:drug effects*; D055432:Metabolomics; D051379:Mice; D008813:Mice, Inbred ICR; D009206:Myocardium / Q000473:pathology; D018517:Plant Roots
chemical_list: D004365:Drugs, Chinese Herbal; D003402:Creatine Kinase