Proteomics and phosphoproteomics analysis of liver in male rats exposed to bisphenol A: Mechanism of hepatotoxicity and biomarker discovery

Food Chem Toxicol. 2018 Feb:112:26-38. doi: 10.1016/j.fct.2017.12.021. Epub 2017 Dec 18.


Bisphenol A (BPA), discovered to be an artificial estrogen, has been shown to leach from some containers and mediate oxidative damage to cells and tissues and to be involved in reproductive disorders, obesity, diabetes, and liver dysfunction. In the current study, we investigated the effects of oral chronic exposure to low dose of BPA (0.5 mg kg-1) on the protein and phosphoprotein expression profiles in male Wistar rat liver using a gel-based proteomics approach based on two-dimensional gel electrophoresis followed by matrix-assisted laser desorption/ionization mass spectrometry identification. Our results showed that BPA exposure affected the levels of proteins and phosphoproteins involved in diverse biological processes associated with hepatotoxicity, fatty liver, and carcinoma. Moreover, we analyzed the effects of BPA on oxidative stress by assessing levels of malondialdehyde (MDA), a marker of lipid peroxidation, and reduced glutathione (GSH), a non-enzymatic antioxidant agent, in the liver. As expected BPA induced oxidative stress indicated by increased levels of MDA and decreased GSH content in the liver. In conclusion, chronic oral exposure of rats to BPA leads to increased oxidative stress in the liver and major alterations in the liver proteome and phosphoproteome, which may contribute to the pathophysiology of liver diseases.

Keywords: Bisphenol A; Hepatotoxicity; Oxidative stress; Phosphoproteomics; Proteomics.

MeSH terms

  • Administration, Oral
  • Animals
  • Benzhydryl Compounds / administration & dosage
  • Benzhydryl Compounds / toxicity*
  • Biomarkers / metabolism*
  • Blotting, Western
  • Chemical and Drug Induced Liver Injury / metabolism
  • Dose-Response Relationship, Drug
  • Electrophoresis, Gel, Two-Dimensional
  • Endocrine Disruptors / administration & dosage
  • Endocrine Disruptors / toxicity*
  • Glutathione / metabolism
  • Lipid Peroxidation / drug effects
  • Liver / drug effects*
  • Liver / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Oxidative Stress / drug effects
  • Phenols / administration & dosage
  • Phenols / toxicity*
  • Phosphoproteins / metabolism*
  • Protein Interaction Maps
  • Proteomics*
  • Rats, Wistar
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods


  • Benzhydryl Compounds
  • Biomarkers
  • Endocrine Disruptors
  • Phenols
  • Phosphoproteins
  • Malondialdehyde
  • Glutathione
  • bisphenol A