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Open AccessEditor’s ChoiceArticle

Biotransformation of the Mycotoxin Zearalenone to its Metabolites Hydrolyzed Zearalenone (HZEN) and Decarboxylated Hydrolyzed Zearalenone (DHZEN) Diminishes its Estrogenicity In Vitro and In Vivo

1
BIOMIN Research Center, Technopark 1, 3430 Tulln, Austria
2
TAmiRNA GmbH, Muthgasse 18, 1190 Vienna, Austria
3
Institute of Applied Genetics and Cell Biology (IAGZ), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad Lorenz-Straße 24, 3430 Tulln, Austria
*
Author to whom correspondence should be addressed.
Toxins 2019, 11(8), 481; https://doi.org/10.3390/toxins11080481
Received: 26 July 2019 / Revised: 9 August 2019 / Accepted: 16 August 2019 / Published: 20 August 2019
(This article belongs to the Special Issue Novel Approaches to Minimising Mycotoxin Contamination)
Zearalenone (ZEN)-degrading enzymes are a promising strategy to counteract the negative effects of this mycotoxin in livestock. The reaction products of such enzymes need to be thoroughly characterized before technological application as a feed additive can be envisaged. Here, we evaluated the estrogenic activity of the metabolites hydrolyzed zearalenone (HZEN) and decarboxylated hydrolyzed zearalenone (DHZEN) formed by hydrolysis of ZEN by the zearalenone-lactonase Zhd101p. ZEN, HZEN, and DHZEN were tested in two in vitro models, the MCF-7 cell proliferation assay (0.01–500 nM) and an estrogen-sensitive yeast bioassay (1–10,000 nM). In addition, we compared the impact of dietary ZEN (4.58 mg/kg) and equimolar dietary concentrations of HZEN and DHZEN on reproductive tract morphology as well as uterine mRNA and microRNA expression in female piglets (n = 6, four weeks exposure). While ZEN increased cell proliferation and reporter gene transcription, neither HZEN nor DHZEN elicited an estrogenic response, suggesting that these metabolites are at least 50–10,000 times less estrogenic than ZEN in vitro. In piglets, HZEN and DHZEN did not increase vulva size or uterus weight. Moreover, RNA transcripts altered upon ZEN treatment (EBAG9, miR-135a-5p, miR-187-3p and miR-204-5p) were unaffected by HZEN and DHZEN. Our study shows that both metabolites exhibit markedly reduced estrogenicity in vitro and in vivo, and thus provides an important basis for further evaluation of ZEN-degrading enzymes. View Full-Text
Keywords: zearalenone; estrogen response element; gene expression; cell proliferation; estrogen receptor; biotransformation zearalenone; estrogen response element; gene expression; cell proliferation; estrogen receptor; biotransformation
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MDPI and ACS Style

Fruhauf, S.; Novak, B.; Nagl, V.; Hackl, M.; Hartinger, D.; Rainer, V.; Labudová, S.; Adam, G.; Aleschko, M.; Moll, W.-D.; Thamhesl, M.; Grenier, B. Biotransformation of the Mycotoxin Zearalenone to its Metabolites Hydrolyzed Zearalenone (HZEN) and Decarboxylated Hydrolyzed Zearalenone (DHZEN) Diminishes its Estrogenicity In Vitro and In Vivo. Toxins 2019, 11, 481. https://doi.org/10.3390/toxins11080481

AMA Style

Fruhauf S, Novak B, Nagl V, Hackl M, Hartinger D, Rainer V, Labudová S, Adam G, Aleschko M, Moll W-D, Thamhesl M, Grenier B. Biotransformation of the Mycotoxin Zearalenone to its Metabolites Hydrolyzed Zearalenone (HZEN) and Decarboxylated Hydrolyzed Zearalenone (DHZEN) Diminishes its Estrogenicity In Vitro and In Vivo. Toxins. 2019; 11(8):481. https://doi.org/10.3390/toxins11080481

Chicago/Turabian Style

Fruhauf, Sebastian; Novak, Barbara; Nagl, Veronika; Hackl, Matthias; Hartinger, Doris; Rainer, Valentina; Labudová, Silvia; Adam, Gerhard; Aleschko, Markus; Moll, Wulf-Dieter; Thamhesl, Michaela; Grenier, Bertrand. 2019. "Biotransformation of the Mycotoxin Zearalenone to its Metabolites Hydrolyzed Zearalenone (HZEN) and Decarboxylated Hydrolyzed Zearalenone (DHZEN) Diminishes its Estrogenicity In Vitro and In Vivo" Toxins 11, no. 8: 481. https://doi.org/10.3390/toxins11080481

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