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Deglucosylation of zearalenone-14-glucoside in animals and human liver leads to underestimation of exposure to zearalenone in humans

(2018) ARCHIVES OF TOXICOLOGY. 92(9). p.2779-2791
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Abstract
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.
Keywords
Zearalenone, Zearalenone-14-glucoside, Metabolism, Modified mycotoxin, II XENOBIOTIC BIOTRANSFORMATION, IN-VITRO, PHASE-I, MASKED MYCOTOXIN, CIS-ZEARALENONE, T-2 TOXIN, LC-HRMS, METABOLISM, RATS, VIVO

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MLA
Yang, Shupeng, Huiyan Zhang, Jinzhen Zhang, et al. “Deglucosylation of Zearalenone-14-glucoside in Animals and Human Liver Leads to Underestimation of Exposure to Zearalenone in Humans.” ARCHIVES OF TOXICOLOGY 92.9 (2018): 2779–2791. Print.
APA
Yang, Shupeng, Zhang, H., Zhang, J., Li, Y., Jin, Y., Zhang, S., De Saeger, S., et al. (2018). Deglucosylation of zearalenone-14-glucoside in animals and human liver leads to underestimation of exposure to zearalenone in humans. ARCHIVES OF TOXICOLOGY, 92(9), 2779–2791.
Chicago author-date
Yang, Shupeng, Huiyan Zhang, Jinzhen Zhang, Yanshen Li, Yue Jin, Suxia Zhang, Sarah De Saeger, et al. 2018. “Deglucosylation of Zearalenone-14-glucoside in Animals and Human Liver Leads to Underestimation of Exposure to Zearalenone in Humans.” Archives of Toxicology 92 (9): 2779–2791.
Chicago author-date (all authors)
Yang, Shupeng, Huiyan Zhang, Jinzhen Zhang, Yanshen Li, Yue Jin, Suxia Zhang, Sarah De Saeger, Yi Li, Jinhui Zhou, Feifei Sun, and Marthe De Boevre. 2018. “Deglucosylation of Zearalenone-14-glucoside in Animals and Human Liver Leads to Underestimation of Exposure to Zearalenone in Humans.” Archives of Toxicology 92 (9): 2779–2791.
Vancouver
1.
Yang S, Zhang H, Zhang J, Li Y, Jin Y, Zhang S, et al. Deglucosylation of zearalenone-14-glucoside in animals and human liver leads to underestimation of exposure to zearalenone in humans. ARCHIVES OF TOXICOLOGY. 2018;92(9):2779–91.
IEEE
[1]
S. Yang et al., “Deglucosylation of zearalenone-14-glucoside in animals and human liver leads to underestimation of exposure to zearalenone in humans,” ARCHIVES OF TOXICOLOGY, vol. 92, no. 9, pp. 2779–2791, 2018.
@article{8582862,
  abstract     = {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.},
  author       = {Yang, Shupeng and Zhang, Huiyan and Zhang, Jinzhen and Li, Yanshen and Jin, Yue and Zhang, Suxia and De Saeger, Sarah and Li, Yi and Zhou, Jinhui and Sun, Feifei and De Boevre, Marthe},
  issn         = {0340-5761},
  journal      = {ARCHIVES OF TOXICOLOGY},
  keywords     = {Zearalenone,Zearalenone-14-glucoside,Metabolism,Modified mycotoxin,II XENOBIOTIC BIOTRANSFORMATION,IN-VITRO,PHASE-I,MASKED MYCOTOXIN,CIS-ZEARALENONE,T-2 TOXIN,LC-HRMS,METABOLISM,RATS,VIVO},
  language     = {eng},
  number       = {9},
  pages        = {2779--2791},
  title        = {Deglucosylation of zearalenone-14-glucoside in animals and human liver leads to underestimation of exposure to zearalenone in humans},
  url          = {http://dx.doi.org/10.1007/s00204-018-2267-z},
  volume       = {92},
  year         = {2018},
}

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