In vivo effects of zearalenone on the expression of proteins involved in the detoxification of rat xenobiotics.
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.
Duca
Radu-Corneliu
RC
DSV/iBiTec-S/SB2SM, CEA Saclay, Gif-sur-Yvette Cedex, France.
Mabondzo
Aloise
A
Bravin
Frédérique
F
Delaforge
Marcel
M
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000818:Animals; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000378:metabolism / Q000633:toxicity*; D006900:Hydroxylation; D008658:Inactivation, Metabolic; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015262:Xenobiotics / Q000378:metabolism / Q000633:toxicity*; D015025:Zearalenone / Q000378:metabolism / Q000633:toxicity*
D018435:ATP Binding Cassette Transporter, Subfamily B; D004968:Estrogens, Non-Steroidal; D012333:RNA, Messenger; D015262:Xenobiotics; D015025:Zearalenone; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1