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.
Highlights
Arsenic is one of the most common metalloid toxicants contaminating groundwater and this contamination is a global concern
We aimed to assess the changes in liver metabolic profile after 96-hr acute exposure to inorganic arsenic (As5+) using gas chromatography coupled with mass spectroscopy (GC/MS)
The protocol was approved by the Institutional Animal Care and Use Committee (IACUC) of the National University of Singapore (Protocol Number: 096/12)
Summary
Arsenic is one of the most common metalloid toxicants contaminating groundwater and this contamination is a global concern. Two inorganic forms of arsenic, trivalent (As3+) and pentavalent (As5+), are the main forms in groundwater, with As5+ as the predominant form in oxidizing conditions [1]. Inorganic arsenic is both acutely and chronically toxic and it is classified as a carcinogen by the International Agency for Research on Cancer [2]. Long-term exposure to arsenic is associated with increased risk of cancers in liver, skin, lungs, bladder and kidney. It can disrupt the cardiovascular, reproduction, nervous system and immune system [3,4,5]. It can disrupt the cardiovascular, reproduction, nervous system and immune system [3,4,5]. 10 μg/L has been set by World Health Organization as the maximal level for arsenic
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