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In vivo effects of zearalenone on the expression of proteins involved in the detoxification of rat xenobiotics
Author(s) -
Duca RaduCorneliu,
Mabondzo Aloise,
Bravin Frédérique,
Delaforge Marcel
Publication year - 2012
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.20617
Subject(s) - pregnane x receptor , cyp3a , biochemistry , monooxygenase , cytochrome p450 , in vivo , biology , hydroxylation , steroid , gene expression , constitutive androstane receptor , xenobiotic , chemistry , metabolism , enzyme , nuclear receptor , gene , transcription factor , microbiology and biotechnology , hormone
Zearalenone (ZEN) is a lactone derivative of the resorcylic acid produced by various Fusarium species that are widely found in foods and animal feeds. ZEN exerts species‐specific estrogenic effects, possibly because of the metabolism differences arising from reduction, hydroxylation, or glucuro‐conjugation. The main objective of this study was to determine the levels of expression of rat proteins that are involved in the ZEN detoxification pathway upon acute ZEN treatment. This was achieved by monitoring the mRNA associated with 25 genes using RT‐PCR upon ZEN uptake. These genes code for a variety of proteins that are involved in cellular detoxifying pathways, transporters, cytochromes P450 (CYPs), hydroxysteroid dehydrogenases, and transferases, and receptors that are involved in CYP expression or steroid metabolism. Liver samples from rats treated with ZEN were compared to untreated rats or animals treated with classical CYP inducers (phenobarbital, dexamethasone, β‐naphtoflavone, and clofibrate). Significant changes of mRNA expression were observed for the efflux transporter, P‐glycoprotein, monooxygenases (CYP2C7, CYP2E1, CYP3A1, CYP3A2, and aromatase), steroid dehydrogenases, and Uridine diphospho–glucuronyl transferases (UGTs). Following a single ZEN treatment, the initial modifications in mRNA levels indicate a close association with microsomal enzyme activity of the CYP2B, CYP2C, and CYP3A protein families. © 2010 Wiley Periodicals, Inc. Environ Toxicol, 2012.