title: Bioactivation of bisphenol A and its analogs (BPF, BPAF, BPZ and DMBPA) in human liver microsomes.
abstract: Bisphenol A analogs are a class of chemicals known as diphenylmethanes, which contain two benzene rings separated by one central carbon atom, usually with a para-hydroxy group on both benzene rings. Bisphenol A (BPA) can induce an uterotrophic response in immature CD-1 mice and elicits estrogenic responses in many other experimental systems. Besides highlighting endocrine effects, a number of metabolic studies provide strong support for the idea that reactive species of BPA are formed in vitro and in vivo that can form covalent adducts with nucleophilic macromolecules and/or produce oxidative stress. We used a liquid chromatography with a triple quadrupole tandem mass spectrometry (LC-MS/MS) for the detection of metabolites and glutathione conjugates of BPA and its analogs (BPF, BPAF, BPZ and DMBPA) in human liver microsomes (HLM) or with recombinant CYP isozymes in the presence of NADPH and GSH as a trapping agent. We have confirmed that BPA and its structural analogs form hydroxylated metabolites and electrophilic species during bioactivation in HLM and CYP isozymes. These results provided important mechanistic insight into the metabolic fate of BPA structural analogs in vitro.
authors.affiliation: University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia.
authors.forename: Jan
authors.initials: J
authors.lastname: Schmidt
authors.forename: Petra
authors.initials: P
authors.lastname: Kotnik
authors.forename: Jurij
authors.initials: J
authors.lastname: Trontelj
authors.forename: Željko
authors.initials: Ž
authors.lastname: Knez
authors.forename: Lucija Peterlin
authors.initials: LP
authors.lastname: Mašič
mesh_terms: D001559:Benzhydryl Compounds / Q000378:metabolism*; D001711:Biotransformation; D002853:Chromatography, Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D052244:Endocrine Disruptors / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism*; D009249:NADP / Q000378:metabolism; D010636:Phenols / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D003577:Cytochrome P-450 Enzyme System; D052244:Endocrine Disruptors; D004967:Estrogens; D005978:Glutathione; D007527:Isoenzymes; D009249:NADP; D010636:Phenols; D011994:Recombinant Proteins; C006780:bisphenol A; D000098826:Bisphenol A Compounds