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Halogenation of common phenolic household and personal care product ingredients enhances their AhR-modulating capacity
ID
Weiss, Veronika
(
Author
),
ID
Gobec, Martina
(
Author
),
ID
Jakopin, Žiga
(
Author
)
URL - Source URL, Visit
https://www.sciencedirect.com/science/article/pii/S0045653524000092
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Abstract
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, 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.
Language:
English
Keywords:
aryl hydrocarbon receptor
,
halogenated transformation products
,
parabens
,
bisphenols
,
UV filters
,
cytokine release
Typology:
1.01 - Original Scientific Article
Organization:
FFA - Faculty of Pharmacy
Publication version:
Version of Record
Publication date:
01.01.2024
Year:
2024
Number of pages:
9 str.
Numbering:
Vol. 350ǂ, art. 141116
PID:
20.500.12556/RUL-154020
UDC:
612.43:620.266.1:616-097
ISSN on article:
0045-6535
DOI:
10.1016/j.chemosphere.2024.141116
COBISS.SI-ID:
179509251
Publication date in RUL:
19.01.2024
Views:
183
Downloads:
7
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Record is a part of a journal
Title:
Chemosphere
Shortened title:
Chemosphere
Publisher:
Pergamon Press.
ISSN:
0045-6535
COBISS.SI-ID:
25213696
Licences
License:
CC BY-NC 4.0, Creative Commons Attribution-NonCommercial 4.0 International
Link:
http://creativecommons.org/licenses/by-nc/4.0/
Description:
A creative commons license that bans commercial use, but the users don’t have to license their derivative works on the same terms.
Secondary language
Language:
Slovenian
Keywords:
arilni ogljikovodikov receptor
,
halogenirani transformacijski produkti
,
parabeni
,
bisfenoli
,
UV filtri
,
sprostitev citokinov
Projects
Funder:
ARIS - Slovenian Research and Innovation Agency
Project number:
P1-0420-2022
Name:
Napredna imunološka zdravila in celični pristopi v farmaciji
Funder:
Other - Other funder or multiple funders
Funding programme:
Ministrstvo za izobraževanje, znanost in šport
Project number:
MR51882
Name:
Ministry of Education, Science, and Sport (MIZŠ) and the European Regional Development Fund OP20.05187 RI-SI-EATRIS
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