Using bisphenol A and its analogs to address the feasibility and usefulness of the CALUX-PPARγ assay to identify chemicals with obesogenic potential.

Autor: Dusserre C; Université Paris Descartes, Faculté de Pharmacie de Paris, Paris 75006, France., Mollergues J; Nestlé Research, Route du Jorat 57, Lausanne 26 CH-1000, Switzerland., Lo Piparo E; Nestlé Research, Route du Jorat 57, Lausanne 26 CH-1000, Switzerland., Smieško M; Molecular Modeling Group, Department of Pharmaceutical Sciences, University of Basel, Klingelbergstrasse 50, CH-4056 Basel, Switzerland., Marin-Kuan M; Nestlé Research, Route du Jorat 57, Lausanne 26 CH-1000, Switzerland., Schilter B; Nestlé Research, Route du Jorat 57, Lausanne 26 CH-1000, Switzerland., Fussell K; Nestlé Research, Route du Jorat 57, Lausanne 26 CH-1000, Switzerland. Electronic address: karma.fussell@rdls.nestle.com.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2018 Dec; Vol. 53, pp. 208-221. Date of Electronic Publication: 2018 Aug 20.
DOI: 10.1016/j.tiv.2018.08.008
Abstrakt: Environmental chemical exposures have been implicated in the obesity epidemic as potential mis-regulators of a variety of metabolic pathways. As agonism of the peroxisome proliferator-activated nuclear hormone receptor γ (PPARγ) is one of the suspected mechanisms involved, a PPARγ screening assay may have relevance for the biodetection of such effects of environmental chemicals. To test this hypothesis, we established the PPARγ 2 -CALUX® assay in-house and tested it against a number of known and suspected PPARγ modulators. Furthermore, we added a rat liver S9 metabolizing system to the protocol to introduce metabolic competence to the assay. Our results confirmed the responsiveness of the cell line to the known PPARγ agonists and antagonists: rosiglitazone, tributyltin, 15-deoxy-Δ 12,14 -prostaglandin J2, GW9662 and diclofenac. These data are in agreement with previous studies in various models. Seven bisphenol analogs tested induced little to no agonist activity, but all demonstrated antagonistic properties. These findings were contrary to both our assumptions and literature reports. Addition of the S9-metabolizing system to each of these tests did not alter any of the measured activities. Taken together, it seems probable that there are additional obesogenic effects of these chemicals which would not be detected by this assay.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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