PUBLICATION

Metabolomic Characterizations of Liver Injury Caused by Acute Arsenic Toxicity in Zebrafish

Authors
Li, C., Li, P., Tan, Y.M., Lam, S.H., Chan, E.C., Gong, Z.
ID
ZDB-PUB-160312-2
Date
2016
Source
PLoS One   11: e0151225 (Journal)
Registered Authors
Gong, Zhiyuan, Lam, Siew Hong
Keywords
Arsenic, Bilirubin, Metabolites, Fatty acids, Zebrafish, Arsenates, Glycolysis, Bile
MeSH Terms
  • Alanine Transaminase/metabolism
  • Animals
  • Arsenic/toxicity*
  • Bile Acids and Salts/metabolism
  • Bilirubin/analysis
  • Biomarkers/analysis
  • Chemical and Drug Induced Liver Injury/etiology
  • Chemical and Drug Induced Liver Injury/physiopathology*
  • Cholic Acid/analysis
  • Cluster Analysis
  • Energy Metabolism/drug effects
  • Gas Chromatography-Mass Spectrometry
  • Glycolysis/drug effects
  • Glycylglycine/analysis
  • Liver/drug effects*
  • Liver/metabolism
  • Liver/pathology
  • Metabolome/drug effects*
  • Principal Component Analysis
  • Taurine/analogs & derivatives
  • Taurine/analysis
  • Zebrafish/metabolism*
PubMed
26967897 Full text @ PLoS One
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping