Last piece in the puzzle of bisphenols BPA, BPS and BPF metabolism : kinetics of the in vitro sulfation reaction

Durcik, Martina (avtor), Gramec, Darja (avtor), Tomašič, Tihomir (avtor), Trontelj, Jurij (avtor), Peterlin-Mašič, Lucija (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: bisphenol sulfates, sulfation kinetics, sulfate estrogenic activity, sulfate stability
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2022
• Št. strani: 9 str.
• Številčenje: Vol. 303, pt. 2, art. 135133
• PID: 20.500.12556/RUL-139674
• UDK: 612.43:620.266.1
• ISSN pri članku: 0045-6535
• DOI: 10.1016/j.chemosphere.2022.135133
• COBISS.SI-ID: 111924227
• Datum objave v RUL: 06.09.2022

Gradivo je del revije

• Naslov: Chemosphere
• Skrajšan naslov: Chemosphere
• Založnik: Elsevier
• ISSN: 0045-6535
• COBISS.SI-ID: 25213696

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: bisfenol sulfati, kinetika sulfacije, sulfatna estrogenska aktivnost, obstojnost sulfatov, hormonski motilci

Projekti

• Financer: ARRS - Agencija za raziskovalno dejavnost Republike Slovenije
• Številka projekta: P1-0208
• Naslov: Farmacevtska kemija: načrtovanje, sinteza in vrednotenje učinkovin