title: An in vitro metabolomics approach to identify hepatotoxicity biomarkers in human L02 liver cells treated with pekinenal, a natural compound.
abstract: 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.
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Pharmacy College, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China.
authors.forename: Jiexia
authors.initials: J
authors.lastname: Shi
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Pharmacy College, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Pharmacy College, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China. hongyuema@126.com.
authors.forename: Hongyue
authors.initials: H
authors.lastname: Ma
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, M5S3E1, Canada.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Guo
authors.affiliation: Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, 160 College Street, Toronto, ON, M5S3E1, Canada.
authors.forename: Zuyao
authors.initials: Z
authors.lastname: Ni
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Pharmacy College, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China. duanja@163.com.
authors.forename: Jin'ao
authors.initials: J
authors.lastname: Duan
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Pharmacy College, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Tao
authors.affiliation: Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, Pharmacy College, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210023, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Qian
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015415:Biomarkers / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D004224:Diterpenes / Q000009:adverse effects*; D028481:Euphorbia / Q000737:chemistry; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D055432:Metabolomics / Q000379:methods*; D009336:Necrosis; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004224:Diterpenes; D005227:Fatty Acids; D017382:Reactive Oxygen Species; C546733:pekinenal
keywords: Human liver cell line L02; Metabolomics; Pekinenal; Signaling pathways; Toxicity biomarkers