20.500.12556/RUL-139674 Last piece in the puzzle of bisphenols BPA, BPS and BPF metabolism kinetics of the in vitro sulfation reaction Bisphenols are endocrine-disrupting chemicals ubiquitously present in the environment, with the consequent exposure to humans. In humans, bisphenols are metabolized to glucuronide and sulfate conjugates. Recent studies indicate that sulfation represents an important bisphenol metabolic pathway for the most vulnerable humans, such as the growing fetus. Our aim was to evaluate sulfation kinetics of commonly detected bisphenols in biological samples: bisphenol A (BPA), bisphenol S (BPS), and bisphenol F (BPF). Furthermore, we evaluated estrogenic agonist potencies and long-term stability of these bisphenol sulfates. BPS and BPF sulfates were prepared by chemical synthesis. Sulfation kinetics of the selected bisphenols were tested in pooled human liver cytosol, as a source for soluble phase II enzymes, including liver sulfotransferases, with quantification by LC-MS/MS. A validated transactivation assay using the hERα-Hela 9903 cell line was used to determine estrogenic agonist potencies. Moreover, BPA, BPS, and BPF sulfate stabilities were examined under various conditions and during storage. In vitro sulfation of BPA and BPS followed Michaelis–Menten kinetics; BPF sulfation followed a substrate inhibition model. Sulfation rates were comparable for these bisphenols, although their K$_M$ values indicated some large differences in affinities. BPA and BPS sulfates are not hERα agonists. The bisphenol sulfates can be considered stable for at least 2 days under these tested media conditions. These data indicate that bisphenol sulfation is an important route in their biotransformation. Compared to glucuronidation, these bisphenols show slower sulfation rates but similar K$_M$ values. BPA and BPS metabolic biotransformation by sulfation provides their detoxification as they are without estrogenic activities. bisphenol sulfates sulfation kinetics sulfate estrogenic activity sulfate stability bisfenol sulfati kinetika sulfacije sulfatna estrogenska aktivnost obstojnost sulfatov hormonski motilci true false true Angleški jezik Slovenski jezik Članek v reviji 2022-09-06 09:32:58 2022-09-06 09:33:03 2022-09-28 08:58:22 0000-00-00 00:00:00 2022 0 0 9 str. pt. 2, art. 135133 Vol. 303 2022 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 612.43:620.266.1 0045-6535 10.1016/j.chemosphere.2022.135133 111924227 1-s2.0-S0045653522016265-main.pdf 1-s2.0-S0045653522016265-main.pdf 1 FCD0E1BDA5DD2E9334B53708E450A57D 80418cf06ce684301e511da92ef39aea2efd19dd5f6c771deaca6b45bd3535ef 71c4d248-2db6-11ed-92af-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=160268 https://www.sciencedirect.com/science/article/pii/S0045653522016265 0 17ab8e22-2db6-11ed-92af-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=160267 Fakulteta za farmacijo 0 0 0