title: 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.
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.
authors.affiliation: UMR 1331 TOXALIM (Research Centre in Food Toxicology), Institut National de la Recherche Agronomique (INRA), Laboratory of Xenobiotic's Cellular and Molecular Toxicology, 400 route des Chappes, BP167, 06903 Sophia-Antipolis Cedex, France. Electronic address: ludovic.peyre@sophia.inra.fr.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Peyre
authors.affiliation: UMR 1331 TOXALIM (Research Centre in Food Toxicology), Institut National de la Recherche Agronomique (INRA), 180 chemin de Tournefeuille, 31027 Toulouse, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Rouimi
authors.affiliation: UMR 1331 TOXALIM (Research Centre in Food Toxicology), Institut National de la Recherche Agronomique (INRA), Laboratory of Xenobiotic's Cellular and Molecular Toxicology, 400 route des Chappes, BP167, 06903 Sophia-Antipolis Cedex, France.
authors.forename: Georges
authors.initials: G
authors.lastname: de Sousa
authors.affiliation: UMR 1331 TOXALIM (Research Centre in Food Toxicology), Institut National de la Recherche Agronomique (INRA), 180 chemin de Tournefeuille, 31027 Toulouse, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Héliès-Toussaint
authors.affiliation: UMR 1331 TOXALIM (Research Centre in Food Toxicology), Institut National de la Recherche Agronomique (INRA), 180 chemin de Tournefeuille, 31027 Toulouse, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Carré
authors.affiliation: Neomah, Research in Toxicology, INRA-Agrobiotech, 06903 Sophia-Antipolis, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Barcellini
authors.affiliation: Nutox Laboratory, Derttech "Packtox", INSERM UMR866, AgroSupDijon, bâtiment Epicure, 1 esplanade Erasme, 21000 Dijon, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Chagnon
authors.affiliation: UMR 1331 TOXALIM (Research Centre in Food Toxicology), Institut National de la Recherche Agronomique (INRA), Laboratory of Xenobiotic's Cellular and Molecular Toxicology, 400 route des Chappes, BP167, 06903 Sophia-Antipolis Cedex, France; UMR 1331 TOXALIM (Research Centre in Food Toxicology), Institut National de la Recherche Agronomique (INRA), 180 chemin de Tournefeuille, 31027 Toulouse, France. Electronic address: Roger.rahmani@sophia.inra.fr.
authors.forename: Roger
authors.initials: R
authors.lastname: Rahmani
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D001559:Benzhydryl Compounds / Q000633:toxicity*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D054890:Fatty Acid Synthase, Type I / Q000235:genetics / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects*; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000166:cytology / Q000187:drug effects; D065626:Non-alcoholic Fatty Liver Disease / Q000473:pathology*; D000070778:Perilipin-1; D010636:Phenols / Q000633:toxicity*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000235:genetics / Q000378:metabolism; D013450:Sulfones / Q000633:toxicity*; D000098831:Bisphenol S Compounds; D000098826:Bisphenol A Compounds
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D001559:Benzhydryl Compounds; D002352:Carrier Proteins; D065702:Cytochrome P-450 CYP2B6; D051544:Cytochrome P-450 CYP3A; D054890:Fatty Acid Synthase, Type I; D005982:Glutathione Transferase; D000070778:Perilipin-1; D010636:Phenols; D010750:Phosphoproteins; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D013450:Sulfones; C513055:ABCB1 protein, human; C543008:bisphenol S; D000098831:Bisphenol S Compounds; C585599:CYP2B6 protein, human; C510163:CYP3A4 protein, human; C518729:FASN protein, human; C041116:leukotriene-C4 synthase; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenols A and S; Diethylstilbestrol; Liver; Metabolism; Pregnane X receptor; Steatosis