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Halogenation of common phenolic household and personal care product ingredients enhances their AhR-modulating capacityWeiss, Veronika, farmacevtka ; Gobec, Martina, 1983- ; Jakopin, ŽigaThe 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, Cl2BPAF with an EC50 of 13 μM. Moreover, our study identified several AhR antagonists, with BrBzP emerging as the most potent with an IC50 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. Cl2BPAF 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 Cl2BPAF 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.Vir: Chemosphere. - ISSN 0045-6535 (Vol. 350, [art. no. 141116], 2024, 9 str.)Vrsta gradiva - članek, sestavni del ; neleposlovje za odrasleLeto - 2024Jezik - angleškiCOBISS.SI-ID - 179509251
Avtor
Weiss, Veronika, farmacevtka |
Gobec, Martina, 1983- |
Jakopin, Žiga
Teme
Hormonski motilci |
Imunski odziv |
aryl hydrocarbon receptor |
halogenated transformation products |
parabens |
bisphenols |
UV filters |
cytokine release |
arilni ogljikovodikov receptor |
halogenirani transformacijski produkti |
parabeni |
bisfenoli |
UV filtri |
sprostitev citokinov
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Avtor | Weiss, Veronika, farmacevtka ; Gobec, Martina, 1983- ; Jakopin, Žiga |
Naslov | Halogenation of common phenolic household and personal care product ingredients enhances their AhR-modulating capacity |
Datum objave | |
COBISS.SI-ID | 179509251 |
Verzija objave v repozitoriju | Založnikova različica |
Licenca objave v repozitoriju | Creative Commons Priznanje avtorstva-Nekomercialno 4.0 Mednarodna |
Embargo | Takojšnja javna objava |
Projekti, iz katerih je bila financirana objava
Naziv | Akronim | Številka projekta | Financer |
---|---|---|---|
Napredna imunološka zdravila in celični pristopi v farmaciji | P1-0420-2022 |
Javna agencija za znanstvenoraziskovalno in inovacijsko dejavnost Republike Slovenije |
|
Young Researcher's programme | 54787 | ||
Ministry of Education, Science, and Sport (MIZŠ) and the European Regional Development Fund OP20.05187 RI-SI-EATRIS | MR51882 |
Ministrstvo za izobraževanje, znanost in šport |
Datoteke, ki spadajo k objavi
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Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
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Weiss, Veronika, farmacevtka | 54787 |
Gobec, Martina, 1983- | 32034 |
Jakopin, Žiga | 26496 |
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