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.

To explore differences of zearalenone (ZEN) metabolism between various species, phase I and II metabolism by liver microsomes of animals and human were investigated using ultra high-pressure liquid chromatography-quadrupole/time-of-flight mass spectrometry (UHPLC-Q/TOF MS). A total of 24 metabolites were identified, among which 12 were reported for the first time. Reduction, hydroxylation, and glucuronidation were the major metabolic pathways of ZEN, and significant differences in various species were also observed. Reduction was the main reaction in swine and human, whereas hydroxylation was predominant in rats, chickens, goats, and cows in in vitro systems. Furthemore, in vivo metabolism of ZEN in rats and chickens was investigated, and 23 and 6 metabolites were identified in each species, respectively. Reduction, hydroxylation, and glucuronidation were the major metabolic pathways in rats, while reduction and sulfation predominated in chickens. These results further enrich the biotransformation profile of ZEN, providing a helpful reference for assessing the risks to animals and humans.

[1]  Efsa Panel on Dietetic Products.  General scientific guidance for stakeholders on health claim applications , 2016 .

[2]  F. Berthiller,et al.  Metabolism of Zearalenone and Its Major Modified Forms in Pigs , 2017, Toxins.

[3]  Suxia Zhang,et al.  Comprehensive Analysis of Tiamulin Metabolites in Various Species of Farm Animals Using Ultra-High-Performance Liquid Chromatography Coupled to Quadrupole/Time-of-Flight. , 2017, Journal of agricultural and food chemistry.

[4]  S. Dänicke,et al.  Zearalenone (ZEN) and ZEN metabolites in feed, urine and bile of sows: Analysis, determination of the metabolic profile and evaluation of the binding forms , 2016 .

[5]  A. Mally,et al.  Biomonitoring of the mycotoxin Zearalenone: current state-of-the art and application to human exposure assessment , 2016, Archives of Toxicology.

[6]  S. Kersten,et al.  Determination of zearalenone, deoxynivalenol and metabolites in bile of piglets fed diets with graded levels of Fusarium toxin contaminated maize , 2016 .

[7]  M. Koch,et al.  Estrogenicity of novel phase I and phase II metabolites of zearalenone and cis-zearalenone. , 2015, Toxicon : official journal of the International Society on Toxinology.

[8]  Suxia Zhang,et al.  Unraveling the in vitro and in vivo metabolism of diacetoxyscirpenol in various animal species and human using ultrahigh-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry , 2015, Analytical and Bioanalytical Chemistry.

[9]  J. Mañes,et al.  Occurrence of Fusarium mycotoxins and their dietary intake through beer consumption by the European population. , 2015, Food chemistry.

[10]  N. Olea,et al.  Zearalenone and its metabolites in urine and breast cancer risk: a case-control study in Tunisia. , 2015, Chemosphere.

[11]  P. de Backer,et al.  Comparative toxicokinetics, absolute oral bioavailability, and biotransformation of zearalenone in different poultry species. , 2015, Journal of Agricultural and Food Chemistry.

[12]  E. Ropstad,et al.  Biotransformation of zearalenone and zearalenols to their major glucuronide metabolites reduces estrogenic activity. , 2015, Toxicology in vitro : an international journal published in association with BIBRA.

[13]  Suxia Zhang,et al.  In vitro and in vivo metabolism of ochratoxin A: a comparative study using ultra-performance liquid chromatography-quadrupole/time-of-flight hybrid mass spectrometry , 2015, Analytical and Bioanalytical Chemistry.

[14]  A. Shan,et al.  Biochemical changes and oxidative stress induced by zearalenone in the liver of pregnant rats , 2015, Human & experimental toxicology.

[15]  Mariana F. Fernández,et al.  Assessment of estrogenic and anti-androgenic activities of the mycotoxin zearalenone and its metabolites using in vitro receptor-specific bioassays. , 2014, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[16]  M. Koch,et al.  In vitro phase I metabolism of cis-zearalenone. , 2014, Chemical research in toxicology.

[17]  Suxia Zhang,et al.  In Vitro and in Vivo Metabolite Profiling of Valnemulin Using Ultraperformance Liquid Chromatography–Quadrupole/Time-of-Flight Hybrid Mass Spectrometry , 2014, Journal of agricultural and food chemistry.

[18]  Jianhong Xu,et al.  Natural occurrence of deoxynivalenol and zearalenone in wheat from Jiangsu province, China. , 2014, Food chemistry.

[19]  S. Kersten,et al.  Residues of zearalenone (ZEN), deoxynivalenol (DON) and their metabolites in plasma of dairy cows fed Fusarium contaminated maize and their relationships to performance parameters. , 2014, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[20]  A. Visconti,et al.  Validation study on urinary biomarkers of exposure for aflatoxin B1, ochratoxin A, fumonisin B1, deoxynivalenol and zearalenone in piglets , 2013 .

[21]  J. Zentek,et al.  The levels of zearalenone and its metabolites in plasma, urine and faeces of horses fed with naturally, Fusarium toxin-contaminated oats. , 2013, Journal of animal physiology and animal nutrition.

[22]  V. Vandenbroucke,et al.  Toxicokinetic study and absolute oral bioavailability of deoxynivalenol, T-2 toxin and zearalenone in broiler chickens. , 2013, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[23]  M. Metzler,et al.  Hydroxylation of the mycotoxin zearalenone at aliphatic positions: novel mammalian metabolites , 2011, Mycotoxin Research.

[24]  M. Metzler,et al.  Absorption and metabolism of the mycotoxin zearalenone and the growth promotor zeranol in Caco-2 cells in vitro. , 2011, Molecular nutrition & food research.

[25]  M. Metzler,et al.  Zearalenone and its metabolites as endocrine disrupting chemicals , 2010 .

[26]  M. Metzler,et al.  Identification of an aliphatic epoxide and the corresponding dihydrodiol as novel congeners of zearalenone in cultures of Fusarium graminearum. , 2010, Journal of Agricultural and Food Chemistry.

[27]  M. Metzler,et al.  Glucuronidation of zearalenone, zeranol and four metabolites in vitro: formation of glucuronides by various microsomes and human UDP-glucuronosyltransferase isoforms. , 2010, Molecular nutrition & food research.

[28]  M. Metzler,et al.  Aromatic hydroxylation and catechol formation: a novel metabolic pathway of the growth promotor zeranol. , 2010, Toxicology letters.

[29]  Sang Wook Hwang,et al.  Disposition, Oral Bioavailability, and Tissue Distribution of Zearalenone in Rats at Various Dose Levels , 2009, Journal of toxicology and environmental health. Part A.

[30]  M. Metzler,et al.  Aromatic hydroxylation is a major metabolic pathway of the mycotoxin zearalenone in vitro. , 2009, Molecular nutrition & food research.

[31]  M. Delaforge,et al.  In Vitro Cytochrome P450 Formation of a Mono-Hydroxylated Metabolite of Zearalenone Exhibiting Estrogenic Activities: Possible Occurrence of This Metabolite in Vivo , 2009, International journal of molecular sciences.

[32]  M. Metzler,et al.  Novel oxidative metabolites of the mycoestrogen zearalenone in vitro. , 2007, Molecular nutrition & food research.

[33]  Hans P. van Egmond,et al.  Regulations relating to mycotoxins in food , 2007 .

[34]  Juan Carlos Moltó,et al.  Review on the toxicity, occurrence, metabolism, detoxification, regulations and intake of zearalenone: an oestrogenic mycotoxin. , 2007, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[35]  J. Fink-Gremmels,et al.  Species differences in the hepatic biotransformation of zearalenone. , 2006, Veterinary journal.

[36]  Zengli Yu,et al.  Anti-apoptotic action of zearalenone in MCF-7 cells. , 2005, Ecotoxicology and environmental safety.

[37]  A. Kong,et al.  Induction of phase I, II and III drug metabolism/transport by xenobiotics , 2005, Archives of pharmacal research.

[38]  J. S. Foster,et al.  Signal transduction through the ras/Erk pathway is essential for the mycoestrogen zearalenone‐induced cell‐cycle progression in MCF‐7 cells , 2001, Molecular carcinogenesis.

[39]  H. Trenholm,et al.  Biliary excretion and enterohepatic cycling of zearalenone in immature pigs. , 1993, Toxicology and applied pharmacology.

[40]  J. K. Lin,et al.  Transformation of zearalenone and zearalenol by rat erythrocytes. , 1984, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.