A mechanistic toxicology study to grasp the mechanics of zearalenone estrogenicity: Spotlighting aromatase and the effects of its genetic variability.

Autor: Perugino F; Department of Food and Drug, University of Parma, Parma, Italy; Department of Biology, University of Naples Federico II, Naples, Italy., Pedroni L; Department of Food and Drug, University of Parma, Parma, Italy., Galaverna G; Department of Food and Drug, University of Parma, Parma, Italy., Dall'Asta C; Department of Food and Drug, University of Parma, Parma, Italy., Dellafiora L; Department of Food and Drug, University of Parma, Parma, Italy. Electronic address: luca.dellafiora@unipr.it.
Jazyk: angličtina
Zdroj: Toxicology [Toxicology] 2024 Jan; Vol. 501, pp. 153686. Date of Electronic Publication: 2023 Nov 28.
DOI: 10.1016/j.tox.2023.153686
Abstrakt: Zearalenone (ZEN) is a mycoestrogen produced by Fusarium fungi contaminating cereals and in grain-based products threatening human and animal health due to its endocrine disrupting effects. Germane to the mechanisms of action, ZEN may activate the estrogen receptors and inhibit the estrogens-producing enzyme aromatase (CYP19A1). Both show single nucleotide variants (SNVs) among humans associated with a diverse susceptibility of being activated or inhibited. These variations might modify the endocrine disrupting action of ZEN, requiring dedicated studies to improve its toxicological understanding. This work focused on human aromatase investigating via 3D molecular modelling whether some of the SNVs reported so far (n = 434) may affect the inhibitory potential of ZEN. It has been also calculated the inhibition capability of α-zearalenol, the most prominent and estrogenically potent phase I metabolite of ZEN, toward those aromatase variants with an expected diverse sensitivity of being inhibited by ZEN. The study: i) described SNVs likely associated with a different susceptibility to ZEN and α-zearalenol inhibition - like T310S that is likely more susceptible to inhibition, or D309G and S478F that are possibly inactive variants; ii) proofed the possible existence of inter-individual susceptibility to ZEN; iii) prioritized aromatase variants for future investigations toward a better comprehension of ZEN xenoestrogenicity at an individual level.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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