RESEARCH ARTICLE Metabolomic Characterizations of Liver Injury Caused by Acute Arsenic Toxicity in Zebrafish Caixia Li1, Ping Li1, Yee Min Tan3, Siew Hong Lam1,2, Eric C. Y. Chan3, Zhiyuan Gong1,2* 1 Department of Biological Sciences, National University of Singapore, Singapore, Singapore, 2 NUS Environmental Research Institute, National University of Singapore, Singapore, Singapore, 3 Department of Pharmacy, National University of Singapore, Singapore, Singapore *
[email protected] 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 tox- icity are still lacking and profile studies at metabolic level are very limited. Using gas chro- OPEN ACCESS matography coupled with mass spectroscopy (GC/MS), we first generated metabolomic Citation: Li C, Li P, Tan YM, Lam SH, Chan ECY, profiles from the livers of arsenic-treated zebrafish and identified 34 significantly altered Gong Z (2016) Metabolomic Characterizations of metabolite peaks as potential markers, including four prominent ones: cholic acid, glycylgly- Liver Injury Caused by Acute Arsenic Toxicity in cine, glycine and hypotaurine. Combined results from GC/MS, histological examination and Zebrafish. PLoS ONE 11(3): e0151225. doi:10.1371/ journal.pone.0151225 pathway analyses suggested a series of alterations, including apoptosis, glycogenolysis, changes in amino acid metabolism and fatty acid composition, accumulation of bile acids Editor: Zhan Yin, Chinese Academy of Sciences, CHINA and fats, and disturbance in glycolysis related energy metabolism. The alterations in glycol- ysis partially resemble Warburg effect commonly observed in many cancer cells. However, Received: October 19, 2015 cellular damages were not reflected in two conventional liver function tests performed, Bili- Accepted: February 23, 2016 rubin assay and alanine aminotransferase (ALT) assay, probably because the short arse- Published: March 11, 2016 nate exposure was insufficient to induce detectable damage.