Metabolic Profile of Zearalenone in Liver Microsomes from Different Species and Its in Vivo Metabolism in Rats and Chickens Using Ultra High-Pressure Liquid Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry

Yang, Shupeng; Zhang, Huiyan; Sun, Fengjun; Ruyck, Karl De; Zhang, Jinzhen; Jin, Yue; Li, Yanshen; Wang, Zhanhui; Saeger, Sarah De; Zhou, Jinhui; Li, Yang; Boevre, Marthe De

doi:10.1021/acs.jafc.7b04663

Cited by 37 publications

(30 citation statements)

References 42 publications

(144 reference statements)

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“…ZON-GA and α-ZOL-GA excreted to the mucosal side in the proximal jejunum are thought to flow into the distal intestine with the digestive contents. ZON is also excreted in the bile after glucuronidation in the liver [53]. In general, glucuronides are likely to enter the enterohepatic circulation [39], suggesting that large amounts of ZON-GA and α-ZOL-GA flow into the distal intestine.…”

Section: Discussionmentioning

confidence: 99%

Glucuronidation as a metabolic barrier against zearalenone in rat everted intestine

Ieko

Inoue

Inomata

et al. 2020

The Journal of Veterinary Medical Science

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Zearalenone (ZON), produced by Fusarium fungi, exhibits estrogenic activity. Livestock can be exposed to ZON orally through contaminating feeds such as cereals, leading to reproductive disorders such as infertility and miscarriage via endocrine system disruption. However, the details of ZON metabolism remain unclear, and the mechanism of its toxicity has not been fully elucidated. In this study, we investigated the kinetics of ZON absorption and metabolism in rat segmented everted intestines. ZON absorption was confirmed in each intestine segment 60 min after application to the mucosal buffer at 10 µM. Approximately half of the absorbed ZON was metabolized to α-zearalenol, which tended to be mainly glucuronidated in intestinal cells. In the proximal intestine, most of the glucuronide metabolized by intestinal cells was excreted to the mucosal side, suggesting that the intestine plays an important role as a first drug metabolism barrier for ZON. However, in the distal intestine, ZON metabolites tended to be transported to the serosal side. Glucuronide transported to the serosal side could be carried via the systemic circulation to the local tissues, where it could be reactivated by deconjugation. These results are important with regard to the mechanism of endocrine disruption caused by ZON.

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Section: Discussionmentioning

confidence: 99%

Glucuronidation as a metabolic barrier against zearalenone in rat everted intestine

Ieko

Inoue

Inomata

et al. 2020

The Journal of Veterinary Medical Science

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“…Similar use is prohibited in the European Union and, due to its anabolic effects, it is also a banned substance in sports . Zeranol is also one of several metabolites from the food contaminant zearalenone in humans and animals …”

Section: Hair Analysis Resultsmentioning

confidence: 99%

“…1 Zeranol is also one of several metabolites from the food contaminant zearalenone in humans and animals. [2][3][4] Zearalenone is a Fusarium mycotoxin that has frequently been found worldwide in plant material, which (in turn) results in contamination of animal feed and food products. Animals can be exposed to zearalenone when certain mycotoxin-producing species of the fungi Fusarium colonize cereals and/or pasture.…”

mentioning

confidence: 99%

Discrimination between zeranol and zearalenone exposure using hair analysis. Application to an adverse analytical finding case

Kintz¹,

Ameline²,

Raul³

2018

Drug Testing and Analysis

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“…Hence, the rate of α-hydroxylation, which is comparably high in pigs [ 9 ], influences the toxicological potency of ZEN. Besides reduction, pathways of ZEN metabolism in animals comprise hydroxylation and glucuronidation, whereby major differences between species are observed [ 11 ]. Notably, ZEN undergoes substantial enterohepatic recirculation in pigs prior to its excretion via feces or urine [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Current challenges in the diagnosis of zearalenone toxicosis as illustrated by a field case of hyperestrogenism in suckling piglets

Hennig-Pauka

Koch²,

Schaumberger³

et al. 2018

Porc Health Manag

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BackgroundThe mycotoxin zearalenone (ZEN) causes functional and morphological alterations in reproductive organs of pigs. In the field, diagnosis of ZEN-induced disorders is often challenging, as relevant feed lots are no longer available, or feed analysis results are not conclusive. Here, we report a field case of hyperestrogenism in newborn piglets. Surprisingly, more than 50 fungal metabolites were detected in hay pellets fed to gestating sows, including ZEN and its modified form zearalenone-14-sulfate (ZEN-14-S). Despite the broad contamination range in this unconventional feed component, a definite diagnosis of mycotoxicosis could not be achieved. In this context, current limitations regarding the confirmation of suspected cases of ZEN-induced disorders are discussed, covering both feed analysis and the biomarker approach.Case presentationA piglet producer with 200 sows experienced a sudden increase in suckling piglet losses up to 30% by lower vitality and crushing. Predominant clinical signs were splay legs and signs of hyperestrogenism such as swollen and reddened vulvae in newborn piglets. The first differential diagnosis was ZEN mycotoxicosis although feed batches had not been changed for months with the exception of ground hay pellets, which had been included in the diet five months before. Analysis of hay pellets resulted in a sum value of ZEN and its modified forms of more than 1000 μg/kg, with ZEN-14-S alone accounting for 530 μg/kg. Considering the inclusion rate of 7% in the diet for gestating sows, the severe impact of the additional ZEN load due to the contaminated hay pellets seemed unrealistic but could not be completely excluded either. One month after hay pellets had been removed from the diet no further clinical signs were observed.ConclusionsEnrichment materials and other fibre sources can contain significant amounts of mycotoxins and should be therefore included in feed analysis. Adequate methods for broad spectrum mycotoxin determination, including modified mycotoxins, are important. As highlighted by this field case, there is a need to establish reliable biomarkers for ZEN exposure in pigs. Currently, available biomarkers do not allow a solid prediction of the ZEN intake of pigs under field conditions, which limits their application to experimental studies.

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Metabolic Profile of Zearalenone in Liver Microsomes from Different Species and Its in Vivo Metabolism in Rats and Chickens Using Ultra High-Pressure Liquid Chromatography-Quadrupole/Time-of-Flight Mass Spectrometry

Cited by 37 publications

References 42 publications

Glucuronidation as a metabolic barrier against zearalenone in rat everted intestine

Glucuronidation as a metabolic barrier against zearalenone in rat everted intestine

Discrimination between zeranol and zearalenone exposure using hair analysis. Application to an adverse analytical finding case

Current challenges in the diagnosis of zearalenone toxicosis as illustrated by a field case of hyperestrogenism in suckling piglets

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