Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9955078 | Toxicology in Vitro | 2018 | 48 Pages |
Abstract
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 PPARγ2-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-Î12,14-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.
Keywords
tetrachlorobisphenol ABPSBPFBPAobesogensPC10MEHPRGZTCBPARLUBFDGEHPTEbisphenol F diglycidyl etherU2OSGW9662MXC15dPGJ2TBTtetrabromobisphenol ADcfTBBPATributyltinBDE-47IC50EC50DEHPBBzP15-deoxy-Δ12,14-Prostaglandin J2TZDsBADGEBisphenolsbisphenol A diglycidyl etherBisphenol Fbisphenol SBisphenol AthiazolidinedionesDi(2-ethylhexyl)phthalateDiclofenacrosiglitazoneIn vitro screeninghalf-maximal effective concentrationMetabolismMethoxychlorMono(2-ethylhexyl)phthalatehalf-maximal inhibitory concentrationrelative light unitsCALUX
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Authors
Camille Dusserre, Julie Mollergues, Elena Lo Piparo, Martin Smieško, Maricel Marin-Kuan, Benoit Schilter, Karma Fussell,