
Toxicokinetics of alpha-zearalenol and its masked form in rats and the comparative biotransformation in liver microsomes from different livestock and humans
- Author
- Shupeng Yang (UGent) , Yanshen Li, Marthe De Boevre (UGent) , Sarah De Saeger (UGent) , Jinhui Zhou, Yi Li, Huiyan Zhang and Feifei Sun
- Organization
- Abstract
- Alpha-zearalenol (alpha-ZEL) and its masked form alpha-zearalenol-14 glucoside (alpha-ZEL-14G) have much higher oestrogenic activity than zearalenone. Owing to very limited toxicokinetic and metabolic data, no reference points could be established for risk assessment. To circumvent it, the toxicokinetic, metabolic profiles, and phenotyping of alpha-ZEL and alpha-ZEL-14G were comprehensively investigated in this study. As a result, the plasma concentrations of alpha-ZEL and alpha-ZEL-14G were all below LOQ after oral administration, while after iv injection, both could be significantly bio-transformed into various metabolites. A complete hydrolysis of alpha-ZEL-14G contributed to alpha-ZEL overall toxicity. Additionally, 31 phase I and 10 phase II metabolites of alpha-ZEL, and 9 phase I and 5 phase II metabolites were identified for alpha-ZEL-14G. For alpha-ZEL, hydroxylation, dehydrogenation, and glucuronidation were the major metabolic pathways, while for alpha-ZEL-14G, it was deglycosylation, reduction, hydroxylation, and glucuronidation. Significant metabolic differences were observed for alpha-ZEL and alpha-ZEL-14G in the liver microsomes of rats, chickens, swine, goats, cows and humans. Phenotyping studies indicated that alpha-ZEL and alpha-ZEL-14G were mediated by CYP 3A4, 2C8, and 1A2. Moreover, the deglycosylation of alpha-ZEL-14G was critically mediated by CES-I and CES-II. The acquired data would provide fundamental perspectives for risk evaluation of mycotoxins and their modified forms.
- Keywords
- ABSOLUTE ORAL BIOAVAILABILITY, MYCOTOXIN ZEARALENONE, FUSARIUM, MYCOTOXINS, PHASE-I, METABOLISM, CEREALS, ZERANOL, URINE, Alpha-zearalenol-14 glucoside, Masked mycotoxins, Metabolism, Zearalenone
Downloads
-
(...).pdf
- full text (Published version)
- |
- UGent only
- |
- |
- 2.23 MB
Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-8673129
- MLA
- Yang, Shupeng, et al. “Toxicokinetics of Alpha-Zearalenol and Its Masked Form in Rats and the Comparative Biotransformation in Liver Microsomes from Different Livestock and Humans.” JOURNAL OF HAZARDOUS MATERIALS, vol. 393, 2020, doi:10.1016/j.jhazmat.2019.121403.
- APA
- Yang, S., Li, Y., De Boevre, M., De Saeger, S., Zhou, J., Li, Y., … Sun, F. (2020). Toxicokinetics of alpha-zearalenol and its masked form in rats and the comparative biotransformation in liver microsomes from different livestock and humans. JOURNAL OF HAZARDOUS MATERIALS, 393. https://doi.org/10.1016/j.jhazmat.2019.121403
- Chicago author-date
- Yang, Shupeng, Yanshen Li, Marthe De Boevre, Sarah De Saeger, Jinhui Zhou, Yi Li, Huiyan Zhang, and Feifei Sun. 2020. “Toxicokinetics of Alpha-Zearalenol and Its Masked Form in Rats and the Comparative Biotransformation in Liver Microsomes from Different Livestock and Humans.” JOURNAL OF HAZARDOUS MATERIALS 393. https://doi.org/10.1016/j.jhazmat.2019.121403.
- Chicago author-date (all authors)
- Yang, Shupeng, Yanshen Li, Marthe De Boevre, Sarah De Saeger, Jinhui Zhou, Yi Li, Huiyan Zhang, and Feifei Sun. 2020. “Toxicokinetics of Alpha-Zearalenol and Its Masked Form in Rats and the Comparative Biotransformation in Liver Microsomes from Different Livestock and Humans.” JOURNAL OF HAZARDOUS MATERIALS 393. doi:10.1016/j.jhazmat.2019.121403.
- Vancouver
- 1.Yang S, Li Y, De Boevre M, De Saeger S, Zhou J, Li Y, et al. Toxicokinetics of alpha-zearalenol and its masked form in rats and the comparative biotransformation in liver microsomes from different livestock and humans. JOURNAL OF HAZARDOUS MATERIALS. 2020;393.
- IEEE
- [1]S. Yang et al., “Toxicokinetics of alpha-zearalenol and its masked form in rats and the comparative biotransformation in liver microsomes from different livestock and humans,” JOURNAL OF HAZARDOUS MATERIALS, vol. 393, 2020.
@article{8673129, abstract = {{Alpha-zearalenol (alpha-ZEL) and its masked form alpha-zearalenol-14 glucoside (alpha-ZEL-14G) have much higher oestrogenic activity than zearalenone. Owing to very limited toxicokinetic and metabolic data, no reference points could be established for risk assessment. To circumvent it, the toxicokinetic, metabolic profiles, and phenotyping of alpha-ZEL and alpha-ZEL-14G were comprehensively investigated in this study. As a result, the plasma concentrations of alpha-ZEL and alpha-ZEL-14G were all below LOQ after oral administration, while after iv injection, both could be significantly bio-transformed into various metabolites. A complete hydrolysis of alpha-ZEL-14G contributed to alpha-ZEL overall toxicity. Additionally, 31 phase I and 10 phase II metabolites of alpha-ZEL, and 9 phase I and 5 phase II metabolites were identified for alpha-ZEL-14G. For alpha-ZEL, hydroxylation, dehydrogenation, and glucuronidation were the major metabolic pathways, while for alpha-ZEL-14G, it was deglycosylation, reduction, hydroxylation, and glucuronidation. Significant metabolic differences were observed for alpha-ZEL and alpha-ZEL-14G in the liver microsomes of rats, chickens, swine, goats, cows and humans. Phenotyping studies indicated that alpha-ZEL and alpha-ZEL-14G were mediated by CYP 3A4, 2C8, and 1A2. Moreover, the deglycosylation of alpha-ZEL-14G was critically mediated by CES-I and CES-II. The acquired data would provide fundamental perspectives for risk evaluation of mycotoxins and their modified forms.}}, articleno = {{121403}}, author = {{Yang, Shupeng and Li, Yanshen and De Boevre, Marthe and De Saeger, Sarah and Zhou, Jinhui and Li, Yi and Zhang, Huiyan and Sun, Feifei}}, issn = {{0304-3894}}, journal = {{JOURNAL OF HAZARDOUS MATERIALS}}, keywords = {{ABSOLUTE ORAL BIOAVAILABILITY,MYCOTOXIN ZEARALENONE,FUSARIUM,MYCOTOXINS,PHASE-I,METABOLISM,CEREALS,ZERANOL,URINE,Alpha-zearalenol-14 glucoside,Masked mycotoxins,Metabolism,Zearalenone}}, language = {{eng}}, pages = {{10}}, title = {{Toxicokinetics of alpha-zearalenol and its masked form in rats and the comparative biotransformation in liver microsomes from different livestock and humans}}, url = {{http://dx.doi.org/10.1016/j.jhazmat.2019.121403}}, volume = {{393}}, year = {{2020}}, }
- Altmetric
- View in Altmetric
- Web of Science
- Times cited: