Halogenation of common phenolic household and personal care product ingredients enhances their AhR-modulating capacity

Weiss, Veronika (avtor), Gobec, Martina (avtor), Jakopin, Žiga (avtor)

The Aryl Hydrocarbon Receptor (AhR), a ligand-activated transcription factor, orchestrates responses to numerous structurally diverse endogenous and exogenous ligands. In addition to binding various xenobiotics, AhR also recognizes endocrine disruptors, particularly those featuring chlorinated or brominated aromatic structures. There is limited data available on the impact of common household and personal care product ingredients let alone their halogenated transformation products. Herein we bridge this knowledge gap by preparing a library of chlorinated and brominated parabens, bisphenols, UV filters, and nonylphenols. An evaluation of total of 125 compounds for agonistic and antagonistic activity on AhR unveiled a low micromolar agonist, Cl$_2$BPAF with an EC$_{50}$ of 13 μM. Moreover, our study identified several AhR antagonists, with BrBzP emerging as the most potent with an IC$_{50}$ of 8.9 μM. To further investigate the functional implications of these compounds, we subjected the most potent agonist and antagonist to a functional assay involving cytokine secretion from peripheral blood mononuclear cells and compared their activity with the commercially available agonist and antagonist. Cl$_2$BPAF exhibited an overall immunosuppressive effect by reducing the secretion of proinflammatory cytokines, including IL-6, IFN-γ, and TNF-α, while BrBzP displayed opposite effects, leading to an increase of those cytokines. Notably, the immunomodulatory effects of Cl$_2$BPAF surpassed those of ITE, a bona fide AhR agonist, while the impact of BrBzP exceeded that of CH223191, a bona fide AhR antagonist. In summary, our study underscores the potential influence of halogenated transformation products on the AhR pathway and, consequently, their role in shaping the immune responses.

• Jezik: Angleški jezik
• Ključne besede: aryl hydrocarbon receptor, halogenated transformation products, parabens, bisphenols, UV filters, cytokine release, AhR
• 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: 2024
• Št. strani: 9 str.
• Številčenje: Vol. 350, art. 141116
• PID: 20.500.12556/RUL-154020
• UDK: 612.43:620.266.1:616-097
• ISSN pri članku: 0045-6535
• DOI: 10.1016/j.chemosphere.2024.141116
• COBISS.SI-ID: 179509251
• Datum objave v RUL: 19.01.2024

Gradivo je del revije

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

Licence

• Licenca: CC BY-NC 4.0, Creative Commons Priznanje avtorstva-Nekomercialno 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc/4.0/deed.sl
• Opis: Licenca Creative Commons, ki prepoveduje komercialno uporabo, vendar uporabniki ne rabijo upravljati materialnih avtorskih pravic na izpeljanih delih z enako licenco.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: arilni ogljikovodikov receptor, halogenirani transformacijski produkti, parabeni, bisfenoli, UV filtri, sprostitev citokinov, hormonski motilci, imunski odziv