PMID- 30019167 OWN - NLM STAT- MEDLINE DCOM- 20191114 LR - 20200114 IS - 1432-0738 (Electronic) IS - 0340-5761 (Linking) VI - 92 IP - 9 DP - 2018 Sep TI - Deglucosylation of zearalenone-14-glucoside in animals and human liver leads to underestimation of exposure to zearalenone in humans. PG - 2779-2791 LID - 10.1007/s00204-018-2267-z [doi] AB - Zearalenone-14-glucoside (ZEN-14G), the modified mycotoxin of zearalenone (ZEN), has attracted considerable attention due to its high potential to be hydrolyzed into ZEN, which would exert toxicity. It has been confirmed that the microflora could metabolize ZEN-14G to ZEN. However, the metabolic profile of ZEN-14G and whether it could be deglucosidated in the liver are unknown. To thoroughly investigate the metabolism of ZEN-14G, in vitro metabolism including phase I and phase II metabolism was studied using liquid chromatography coupled to high-resolution mass spectrometry. Additionally, in vivo metabolism of ZEN-14G was conducted in model animals, rats, by oral administration. As a result, 29 phase I metabolites and 6 phase II metabolites were identified and significant inter-species metabolic differences were observed as well. What is more, ZEN-14G could be considerably deglucosidated into its free form of ZEN after the incubation with animals and human liver microsomes in the absence of NADPH, which was mainly metabolized by human carboxylesterase CES-I and II. Furthermore, results showed that the major metabolic pathways of ZEN-14G were deglucosylation, hydroxylation, hydrogenation and glucuronidation. Although interspecies differences in the biotransformation of ZEN-14G were observed, ZEN, alpha-ZEL-14G, beta-ZEL-14G, alpha-ZEL, ZEN-14G-16GlcA and ZEN-14GlcA were the major metabolites of ZEN-14G. Additionally, a larger yield of 6-OH-ZEN-14G and 8-OH-ZEN-14G was also observed in human liver microsomes. The obtained data would be of great importance for the safety assessment of modified mycotoxin, ZEN-14G, and provide another perspective for risk assessment of mycotoxin. FAU - Yang, Shupeng AU - Yang S AD - Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing, 100093, People's Republic of China. AD - Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium. AD - College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People's Republic of China. FAU - Zhang, Huiyan AU - Zhang H AD - Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium. AD - College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People's Republic of China. FAU - Zhang, Jinzhen AU - Zhang J AD - Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing, 100093, People's Republic of China. FAU - Li, Yanshen AU - Li Y AD - College of Life Science, Yantai University, Yantai, 264005, Shandong, People's Republic of China. FAU - Jin, Yue AU - Jin Y AD - Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing, 100093, People's Republic of China. FAU - Zhang, Suxia AU - Zhang S AD - College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People's Republic of China. FAU - De Saeger, Sarah AU - De Saeger S AD - Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium. FAU - Li, Yi AU - Li Y AD - Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing, 100093, People's Republic of China. FAU - Zhou, Jinhui AU - Zhou J AD - Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing, 100093, People's Republic of China. FAU - Sun, Feifei AU - Sun F AUID- ORCID: 0000-0001-6295-6444 AD - Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Key Laboratory of Bee Products for Quality and Safety Control, Bee Product Quality Supervision and Testing Center, Ministry of Agriculture, Beijing, 100093, People's Republic of China. sun00114@umn.edu. AD - College of Veterinary Medicine, China Agricultural University, Beijing, 100193, People's Republic of China. sun00114@umn.edu. FAU - De Boevre, Marthe AU - De Boevre M AD - Laboratory of Food Analysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium. LA - eng PT - Journal Article DEP - 20180717 PL - Germany TA - Arch Toxicol JT - Archives of toxicology JID - 0417615 RN - 0 (Glucosides) RN - 0 (zearalenone-14-glucoside) RN - 5W827M159J (Zearalenone) SB - IM MH - Animals MH - Chickens MH - Dietary Exposure/*analysis MH - Female MH - Glucosides/*metabolism/*toxicity MH - Goats MH - Humans MH - Hydroxylation MH - Inactivation, Metabolic/drug effects/physiology MH - Male MH - Microsomes, Liver/drug effects/*metabolism MH - Oxidation-Reduction MH - Rats, Wistar MH - Swine MH - Zearalenone/*analogs & derivatives/*metabolism/*toxicity OTO - NOTNLM OT - Metabolism OT - Modified mycotoxin OT - Zearalenone OT - Zearalenone-14-glucoside EDAT- 2018/07/19 06:00 MHDA- 2019/11/15 06:00 CRDT- 2018/07/19 06:00 PHST- 2018/03/14 00:00 [received] PHST- 2018/07/12 00:00 [accepted] PHST- 2018/07/19 06:00 [pubmed] PHST- 2019/11/15 06:00 [medline] PHST- 2018/07/19 06:00 [entrez] AID - 10.1007/s00204-018-2267-z [pii] AID - 10.1007/s00204-018-2267-z [doi] PST - ppublish SO - Arch Toxicol. 2018 Sep;92(9):2779-2791. doi: 10.1007/s00204-018-2267-z. Epub 2018 Jul 17.