title: Metabolomic Characterizations of Liver Injury Caused by Acute Arsenic Toxicity in Zebrafish.
abstract: Arsenic is one of the most common metalloid contaminants in groundwater and it has both acute and chronic toxicity affecting multiple organs. Details of the mechanism of arsenic toxicity are still lacking and profile studies at metabolic level are very limited. Using gas chromatography coupled with mass spectroscopy (GC/MS), we first generated metabolomic profiles from the livers of arsenic-treated zebrafish and identified 34 significantly altered metabolite peaks as potential markers, including four prominent ones: cholic acid, glycylglycine, glycine and hypotaurine. Combined results from GC/MS, histological examination and pathway analyses suggested a series of alterations, including apoptosis, glycogenolysis, changes in amino acid metabolism and fatty acid composition, accumulation of bile acids and fats, and disturbance in glycolysis related energy metabolism. The alterations in glycolysis partially resemble Warburg effect commonly observed in many cancer cells. However, cellular damages were not reflected in two conventional liver function tests performed, Bilirubin assay and alanine aminotransferase (ALT) assay, probably because the short arsenate exposure was insufficient to induce detectable damage. This study demonstrated that metabolic changes could reflect mild liver impairments induced by arsenic exposure, which underscored their potential in reporting early liver injury.
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
authors.forename: Caixia
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore, Singapore.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore, Singapore.
authors.forename: Yee Min
authors.initials: YM
authors.lastname: Tan
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore, Singapore.|NUS Environmental Research Institute, National University of Singapore, Singapore, Singapore.
authors.forename: Siew Hong
authors.initials: SH
authors.lastname: Lam
authors.affiliation: Department of Pharmacy, National University of Singapore, Singapore, Singapore.
authors.forename: Eric C Y
authors.initials: EC
authors.lastname: Chan
authors.affiliation: Department of Biological Sciences, National University of Singapore, Singapore, Singapore.|NUS Environmental Research Institute, National University of Singapore, Singapore, Singapore.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Gong
mesh_terms: D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D001647:Bile Acids and Salts / Q000378:metabolism; D001663:Bilirubin / Q000032:analysis; D015415:Biomarkers / Q000032:analysis; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000503:physiopathology*; D019826:Cholic Acid / Q000032:analysis; D016000:Cluster Analysis; D004734:Energy Metabolism / Q000187:drug effects; D008401:Gas Chromatography-Mass Spectrometry; D006019:Glycolysis / Q000187:drug effects; D006033:Glycylglycine / Q000032:analysis; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D055442:Metabolome / Q000187:drug effects*; D025341:Principal Component Analysis; D013654:Taurine / Q000031:analogs & derivatives / Q000032:analysis; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D001647:Bile Acids and Salts; D015415:Biomarkers; D006033:Glycylglycine; D013654:Taurine; C003949:hypotaurine; D000410:Alanine Transaminase; D019826:Cholic Acid; D001151:Arsenic; D001663:Bilirubin