An in vitro metabolomics approach to identify hepatotoxicity biomarkers in human L02 liver cells treated with pekinenal, a natural compound

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• 作者：Jiexia Shi ; Jing Zhou ; Hongyue Ma ; Hongbo Guo…
• 关键词：Pekinenal ; Toxicity biomarkers ; Signaling pathways ; Metabolomics ; Human liver cell line L02
• 刊名：Analytical and Bioanalytical Chemistry
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：408
• 期：5
• 页码：1413-1424
• 全文大小：2,415 KB
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• 作者单位：Jiexia Shi (1)
  Jing Zhou (1)
  Hongyue Ma (1)
  Hongbo Guo (2)
  Zuyao Ni (2)
  Jin’ao Duan (1)
  Weiwei Tao (1)
  Dawei Qian (1)
  
  1. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Pharmacy College, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China
  2. Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, M5S3E1, Canada
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Analytical Chemistry
  Food Science
  Inorganic Chemistry
  Physical Chemistry
  Monitoring, Environmental Analysis and Environmental Ecotoxicology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1618-2650

文摘

An in vitro cell metabolomics study was performed on human L02 liver cells to investigate the toxic biomarkers of pekinenal from the herb Euphorbia pekinensis Rupr. Pekinenal significantly induced L02 cell damage, which was characterised by necrosis and apoptosis. Metabolomics combined with data pattern recognition showed that pekinenal significantly altered the profiles of more than 1299 endogenous metabolites with variable importance in the projection (VIP) > 1. Further, screening correlation coefficients between the intensities of all metabolites and the extent of L02 cell damage (MTT) identified 12 biomarker hits: ten were downregulated and two were upregulated. Among these hits, LysoPC(18:1(9Z)/(11Z)), PC(22:0/15:0) and PC(20:1(11Z)/14:1(9Z)) were disordered, implying the initiation of inflammation and cell damage. Several fatty acids (FAs) (3-hydroxytetradecanedioic acid, pivaloylcarnitine and eicosapentaenoyl ethanolamide) decreased due to fatty acid oxidation. Dihydroceramide and Cer(d18:0/14:0) were also altered and are associated with apoptosis. Additional examination of the levels of intracellular reactive oxygen species (ROS) and two eicosanoids (PGE2, PGF2α) in the cell supernatant confirmed the fatty acid oxidation and arachidonic acid metabolism pathways, respectively. In summary, cell metabolomics is a highly efficient approach for identifying toxic biomarkers and helping understand toxicity mechanisms and predict herb-induced liver injury.