Comparative study of bisphenol A and its analogue bisphenol S on human hepatic cells: a focus on their potential involvement in nonalcoholic fatty liver disease

Food Chem Toxicol. 2014 Aug:70:9-18. doi: 10.1016/j.fct.2014.04.011. Epub 2014 May 1.

Abstract

For several decades, people have been in contact with bisphenol A (BPA) primarily through their diet. Nowadays it is gradually replaced by an analogue, bisphenol S (BPS). In this study, we compared the effects of these two bisphenols in parallel with the positive control diethylstilbestrol (DES) on different hepatocyte cell lines. Using a cellular impedance system we have shown that BPS is less cytotoxic than BPA in acute and chronic conditions. We have also demonstrated that, contrary to BPA, BPS is not able to induce an increase in intracellular lipid and does not activate the PXR receptor which is known to be involved in part, in this process. In parallel, it failed to modulate the expression of CYP3A4 and CYP2B6, the drug transporter ABCB1 and other lipid metabolism genes (FASN, PLIN). However, it appears to have a weak effect on GSTA4 protein expression and on the Erk1/2 pathway. In conclusion, in contrast to BPA, BPS does not appear to induce the metabolic syndrome that may lead to non-alcoholic fatty liver disease (NAFLD), in vitro. Although we have to pay special attention to BPS, its use could be less dangerous concerning this toxicological endpoint for human health.

Keywords: Bisphenols A and S; Diethylstilbestrol; Liver; Metabolism; Pregnane X receptor; Steatosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • Benzhydryl Compounds / toxicity*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line
  • Cytochrome P-450 CYP2B6 / genetics
  • Cytochrome P-450 CYP2B6 / metabolism
  • Cytochrome P-450 CYP3A / genetics
  • Cytochrome P-450 CYP3A / metabolism
  • Fatty Acid Synthase, Type I / genetics
  • Fatty Acid Synthase, Type I / metabolism
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Hep G2 Cells
  • Hepatocytes / drug effects*
  • Humans
  • Lipid Metabolism / drug effects
  • Liver / cytology
  • Liver / drug effects
  • Non-alcoholic Fatty Liver Disease / pathology*
  • Perilipin-1
  • Phenols / toxicity*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Pregnane X Receptor
  • Receptors, Steroid / genetics
  • Receptors, Steroid / metabolism
  • Sulfones / toxicity*

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • Benzhydryl Compounds
  • Carrier Proteins
  • Perilipin-1
  • Phenols
  • Phosphoproteins
  • Pregnane X Receptor
  • Receptors, Steroid
  • Sulfones
  • bis(4-hydroxyphenyl)sulfone
  • CYP2B6 protein, human
  • Cytochrome P-450 CYP2B6
  • Cytochrome P-450 CYP3A
  • CYP3A4 protein, human
  • FASN protein, human
  • Fatty Acid Synthase, Type I
  • Glutathione Transferase
  • leukotriene-C4 synthase
  • bisphenol A