The metabolomic profiling of serum in rats exposed to arsenic using UPLC/Q-TOF MS

Toxicol Lett. 2014 Sep 17;229(3):474-81. doi: 10.1016/j.toxlet.2014.06.001. Epub 2014 Jun 21.

Abstract

Chronic arsenicosis induced by excessive arsenic intake can cause damages to multi-organ systems, skin cancer and various internal cancers. However, the key metabolic changes and biomarkers which can reflect these changes remain unclear resulting in a lack of effective prevention and treatments. The aim of this study is to determine the impact of chronic arsenic exposure on the metabolism of organism, and find the metabolites changes by using metabolomic techniques. Thirty male Wistar rats were randomly divided into three groups. The arsenite was administered in water, and the doses were 0, 10, and 50mg/L, respectively. The exposure lasted for 6 months. The endogenous metabolite profile of serum was investigated by ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. Partial least squares discriminant analysis (PLS-DA) enabled clusters to be visualized. Nine serum principal metabolites contributing to the clusters were identified, which were CPA (18:2(9Z,12Z)/0:0), LysoPC (14:0), LysoPC (18:4 (6Z,9Z,12Z,15Z)), LysoPC (P-18:0), l-palmitoylcarnitine, LysoPC (20:2(11Z,14Z)) in positive ESI mode and deoxygcholylglycine, LysoPE (0:0/20:2(11Z,14Z)), 15(S)-hydroxyeicosatrienoic acid in negative ESI. These changes of metabolites in rats suggested the changed metabolism in rats exposed to arsenic. These findings may further aid diagnose and serve as targets for therapeutic intervention of arsenicosis.

Keywords: Biomarker; Chronic arsenicosis; Mechanism; Metabonomics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arsenic Poisoning / blood
  • Arsenic Poisoning / metabolism*
  • Arsenites / poisoning
  • Biomarkers / blood
  • Chromatography, High Pressure Liquid / methods
  • Dose-Response Relationship, Drug
  • Male
  • Mass Spectrometry / methods
  • Metabolomics
  • Rats
  • Rats, Wistar

Substances

  • Arsenites
  • Biomarkers
  • arsenite