Screening of chemicals with binding activities of liver X receptors from reclaimed waters

Abstract Wastewater reclamation and reuse is considered an attractive and practical method for coping with water scarcity. However, the presence of micropollutants in reclaimed water, including endocrine disrupting chemicals (EDCs), is a major public health concern. This study attempted to identify unknown EDCs with liver X receptor (LXRα) agonist/antagonist activities in reclaimed wastewater, using nuclear receptors binding extraction coupled with high-resolution mass spectrometry (NRBE-HRMS). In total, 105 compounds in the reclaimed wastewater exhibited LXRα-binding activity. Among them, two previously unknown LXRα-antagonist compounds, catechol and 4-acetamidoantipyrine, were identified, based on authentic standards. The two LXRα-antagonist compounds exhibited weak LXRα-antagonist activities in a yeast two-hybrid assay. Catechol and 4-acetamidoantipyrine inhibited the β-galactosidase activity induced by 60 nM of TO901317 in an LXRα yeast assay, with IC20 values of 79,938.9 nM and 6286.4 nM, respectively. To the best of our knowledge, this is the first study to identify EDCs in reclaimed wastewater with LXRα-agonist/antagonist activity using the NRBE-HRMS method.