Interaction of mycotoxins zearalenone, α-zearalenol, and β-zearalenol with cytochrome P450 (CYP1A2, 2C9, 2C19, 2D6, and 3A4) enzymes and organic anion transporting polypeptides (OATP1A2, OATP1B1, OATP1B3, and OATP2B1).

Autor: Kaci H; Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, HUN-REN, Magyar tudósok krt. 2, Budapest H-1117, Hungary; Doctoral School of Biology, Institute of Biology, Eötvös Loránd University, Pázmány P. stny. 1/C, Budapest H-1117, Hungary., Dombi Á; Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, Pécs H-7624, Hungary., Gömbös P; Institute of Physiology and Nutrition, Department of Physiology and Animal Health, Agribiotechnology and Precision Breeding for Food Security National Laboratory, Hungarian University of Agriculture and Life Sciences, Gödöllő H-2103, Hungary., Szabó A; Institute of Physiology and Nutrition, Department of Physiology and Animal Health, Agribiotechnology and Precision Breeding for Food Security National Laboratory, Hungarian University of Agriculture and Life Sciences, Gödöllő H-2103, Hungary; HUN-REN-MATE Mycotoxins in the Food Chain Research Group, Hungarian University of Agriculture and Life Sciences, Guba Sándor Str. 40, Kaposvár 7400, Hungary., Bakos É; Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, HUN-REN, Magyar tudósok krt. 2, Budapest H-1117, Hungary., Özvegy-Laczka C; Drug Resistance Research Group, Institute of Enzymology, Research Centre for Natural Sciences, HUN-REN, Magyar tudósok krt. 2, Budapest H-1117, Hungary., Poór M; Department of Laboratory Medicine, Medical School, University of Pécs, Ifjúság útja 13, Pécs H-7624, Hungary; Molecular Medicine Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs H-7624, Hungary. Electronic address: poor.miklos@pte.hu.
Jazyk: angličtina
Zdroj: Toxicology in vitro : an international journal published in association with BIBRA [Toxicol In Vitro] 2024 Apr; Vol. 96, pp. 105789. Date of Electronic Publication: 2024 Feb 08.
DOI: 10.1016/j.tiv.2024.105789
Abstrakt: Zearalenone (ZEN) is a mycoestrogen produced by Fusarium fungi. ZEN is a frequent contaminant in cereal-based products, representing significant health threat. The major reduced metabolites of ZEN are α-zearalenol (α-ZEL) and β-zearalenol (β-ZEL). Since the toxicokinetic interactions of ZEN/ZELs with cytochrome P450 enzymes (CYPs) and organic anion transporting polypeptides (OATPs) have been barely characterized, we examined these interactions applying in vitro models. ZEN and ZELs were relatively strong inhibitors of CYP3A4 and moderate inhibitors of CYP1A2 and CYP2C9. Both CYP1A2 and CYP3A4 decreased ZEN and β-ZEL concentrations in depletion assays, while only CYP1A2 reduced α-ZEL levels. OATPs tested were strongly or moderately inhibited by ZEN and ZELs; however, these mycotoxins did not show higher cytotoxicity in OATP-overexpressing cells. Our results help the deeper understanding of the toxicokinetic/pharmacokinetic interactions of ZEN, α-ZEL, and β-ZEL.
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 © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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