In Vitro Cytochrome P450 Formation of a Mono-Hydroxylated Metabolite of Zearalenone Exhibiting Estrogenic Activities: Possible Occurrence of This Metabolite in Vivo
The mycoestrogen zearalenone (ZEN), as well as its reduced metabolites, which belong to the endocrine disruptor bio-molecule family, are substrates for various enzymes involved in steroid metabolism. In addition to its reduction by the steroid dehydrogenase pathway, ZEN also interacts with hepatic d...
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| Format: | Article |
| Language: | English |
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MDPI AG
2009-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/10/4/1824/ |
| _version_ | 1811297078860578816 |
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| author | Marcel Delaforge Radu C. Duca Patrick Balaguer Frederique Bravin |
| author_facet | Marcel Delaforge Radu C. Duca Patrick Balaguer Frederique Bravin |
| author_sort | Marcel Delaforge |
| collection | DOAJ |
| description | The mycoestrogen zearalenone (ZEN), as well as its reduced metabolites, which belong to the endocrine disruptor bio-molecule family, are substrates for various enzymes involved in steroid metabolism. In addition to its reduction by the steroid dehydrogenase pathway, ZEN also interacts with hepatic detoxification enzymes, which convert it into hydroxylated metabolites (OH-ZEN). Due to their structures to that of estradiol, ZEN and its derived metabolites bind to the estrogen receptors and are involved in endocrinal perturbations and are possibly associated with estrogen-dependent cancers. The primary aim of this present study was to identify the enzymatic cytochrome P450 isoforms responsible for the formation of the most abundant OH-ZEN. We thus studied its in vitro formation using hepatic microsomes in a range of animal model systems including man. OH-ZEN was also recovered in liver and urine of rats treated orally with ZEN. Finally we compared the activity of ZEN and its active metabolites (α-ZAL and OH-ZEN) on estrogen receptors using HeLa ER-α and ER-β reporter cell lines as reporters. OH-ZEN estrogenic activities were revealed to be limited and not as significant as those of ZEN or α-ZAL. |
| first_indexed | 2024-04-13T05:58:43Z |
| format | Article |
| id | doaj.art-8b10c626ba8d47b7864eac023f872624 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T05:58:43Z |
| publishDate | 2009-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8b10c626ba8d47b7864eac023f8726242022-12-22T02:59:32ZengMDPI AGInternational Journal of Molecular Sciences1422-00672009-04-011041824183710.3390/ijms10041824In Vitro Cytochrome P450 Formation of a Mono-Hydroxylated Metabolite of Zearalenone Exhibiting Estrogenic Activities: Possible Occurrence of This Metabolite in VivoMarcel DelaforgeRadu C. DucaPatrick BalaguerFrederique BravinThe mycoestrogen zearalenone (ZEN), as well as its reduced metabolites, which belong to the endocrine disruptor bio-molecule family, are substrates for various enzymes involved in steroid metabolism. In addition to its reduction by the steroid dehydrogenase pathway, ZEN also interacts with hepatic detoxification enzymes, which convert it into hydroxylated metabolites (OH-ZEN). Due to their structures to that of estradiol, ZEN and its derived metabolites bind to the estrogen receptors and are involved in endocrinal perturbations and are possibly associated with estrogen-dependent cancers. The primary aim of this present study was to identify the enzymatic cytochrome P450 isoforms responsible for the formation of the most abundant OH-ZEN. We thus studied its in vitro formation using hepatic microsomes in a range of animal model systems including man. OH-ZEN was also recovered in liver and urine of rats treated orally with ZEN. Finally we compared the activity of ZEN and its active metabolites (α-ZAL and OH-ZEN) on estrogen receptors using HeLa ER-α and ER-β reporter cell lines as reporters. OH-ZEN estrogenic activities were revealed to be limited and not as significant as those of ZEN or α-ZAL.http://www.mdpi.com/1422-0067/10/4/1824/Cytochrome P450zearalenonehydroxy-metabolitesestrogenic activitieshuman |
| spellingShingle | Marcel Delaforge Radu C. Duca Patrick Balaguer Frederique Bravin In Vitro Cytochrome P450 Formation of a Mono-Hydroxylated Metabolite of Zearalenone Exhibiting Estrogenic Activities: Possible Occurrence of This Metabolite in Vivo International Journal of Molecular Sciences Cytochrome P450 zearalenone hydroxy-metabolites estrogenic activities human |
| title | In Vitro Cytochrome P450 Formation of a Mono-Hydroxylated Metabolite of Zearalenone Exhibiting Estrogenic Activities: Possible Occurrence of This Metabolite in Vivo |
| title_full | In Vitro Cytochrome P450 Formation of a Mono-Hydroxylated Metabolite of Zearalenone Exhibiting Estrogenic Activities: Possible Occurrence of This Metabolite in Vivo |
| title_fullStr | In Vitro Cytochrome P450 Formation of a Mono-Hydroxylated Metabolite of Zearalenone Exhibiting Estrogenic Activities: Possible Occurrence of This Metabolite in Vivo |
| title_full_unstemmed | In Vitro Cytochrome P450 Formation of a Mono-Hydroxylated Metabolite of Zearalenone Exhibiting Estrogenic Activities: Possible Occurrence of This Metabolite in Vivo |
| title_short | In Vitro Cytochrome P450 Formation of a Mono-Hydroxylated Metabolite of Zearalenone Exhibiting Estrogenic Activities: Possible Occurrence of This Metabolite in Vivo |
| title_sort | in vitro cytochrome p450 formation of a mono hydroxylated metabolite of zearalenone exhibiting estrogenic activities possible occurrence of this metabolite in vivo |
| topic | Cytochrome P450 zearalenone hydroxy-metabolites estrogenic activities human |
| url | http://www.mdpi.com/1422-0067/10/4/1824/ |
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