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In vivo contribution of deoxynivalenol-3-β-D-glucoside to deoxynivalenol exposure in broiler chickens and pigs: oral bioavailability, hydrolysis and toxicokinetics

(2017) ARCHIVES OF TOXICOLOGY. 91(2). p.699-712
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Abstract
Crossover animal trials were performed with intravenous and oral administration of deoxynivalenol-3-β-D-glucoside (DON3G) and deoxynivalenol (DON) to broiler chickens and pigs. Systemic plasma concentrations of DON, DON3G and de-epoxy-DON were quantified using liquid chromatography-tandem mass spectrometry. Liquid chromatography coupled to high-resolution mass spectrometry was used to unravel phase II metabolism of DON. Additionally for pigs, portal plasma was analysed to study presystemic hydrolysis and metabolism. Data were processed via tailor-made compartmental toxicokinetic models. The results in broiler chickens indicate that DON3G is not hydrolysed to DON in vivo. Furthermore, the absolute oral bioavailability of DON3G in broiler chickens was low (3.79 ± 2.68 %) and comparable to that of DON (5.56 ± 2.05 %). After PO DON3G administration to pigs, only DON was detected in plasma, indicating a complete presystemic hydrolysis of the absorbed fraction of DON3G. However, the absorbed fraction of DON3G, recovered as DON, was approximately 5 times lower than after PO DON administration, 16.1 ± 5.4 compared with 81.3 ± 17.4 %. Analysis of phase II metabolites revealed that biotransformation of DON and DON3G in pigs mainly consists of glucuronidation, whereas in chickens predominantly conjugation with sulphate occurred. The extent of phase II metabolism is notably higher for chickens than for pigs, which might explain the differences in sensitivity of these species to DON. Although in vitro studies demonstrate a decreased toxicity of DON3G compared with DON, the species-dependent toxicokinetic data and in vivo hydrolysis to DON illustrate the toxicological relevance and consequently the need for further research to establish a tolerable daily intake.
Keywords
Masked mycotoxins, Modified mycotoxins, Animal trials, Fusarium toxins, MASKED MYCOTOXIN DEOXYNIVALENOL-3-GLUCOSIDE, UDP-GLUCOSYLTRANSFERASE, MASS-SPECTROMETRY, VITRO DIGESTION, T-2 TOXIN, METABOLISM, GUT, ZEARALENONE, ABSORPTION, EXCRETION

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Citation

Please use this url to cite or link to this publication:

Chicago
Broekaert, Nathan, Mathias Devreese, Thomas van Bergen, Stijn Schauvliege, Marthe De Boevre, Sarah De Saeger, Lynn Vanhaecke, et al. 2017. “In Vivo Contribution of deoxynivalenol-3-β-D-glucoside to Deoxynivalenol Exposure in Broiler Chickens and Pigs: Oral Bioavailability, Hydrolysis and Toxicokinetics.” Archives of Toxicology 91 (2): 699–712.
APA
Broekaert, N., Devreese, M., van Bergen, T., Schauvliege, S., De Boevre, M., De Saeger, S., Vanhaecke, L., et al. (2017). In vivo contribution of deoxynivalenol-3-β-D-glucoside to deoxynivalenol exposure in broiler chickens and pigs: oral bioavailability, hydrolysis and toxicokinetics. ARCHIVES OF TOXICOLOGY, 91(2), 699–712.
Vancouver
1.
Broekaert N, Devreese M, van Bergen T, Schauvliege S, De Boevre M, De Saeger S, et al. In vivo contribution of deoxynivalenol-3-β-D-glucoside to deoxynivalenol exposure in broiler chickens and pigs: oral bioavailability, hydrolysis and toxicokinetics. ARCHIVES OF TOXICOLOGY. 2017;91(2):699–712.
MLA
Broekaert, Nathan, Mathias Devreese, Thomas van Bergen, et al. “In Vivo Contribution of deoxynivalenol-3-β-D-glucoside to Deoxynivalenol Exposure in Broiler Chickens and Pigs: Oral Bioavailability, Hydrolysis and Toxicokinetics.” ARCHIVES OF TOXICOLOGY 91.2 (2017): 699–712. Print.
@article{7192881,
  abstract     = {Crossover animal trials were performed with intravenous and oral administration of deoxynivalenol-3-\ensuremath{\beta}-D-glucoside (DON3G) and deoxynivalenol (DON) to broiler chickens and pigs. Systemic plasma concentrations of DON, DON3G and de-epoxy-DON were quantified using liquid chromatography-tandem mass spectrometry. Liquid chromatography coupled to high-resolution mass spectrometry was used to unravel phase II metabolism of DON. Additionally for pigs, portal plasma was analysed to study presystemic hydrolysis and metabolism. Data were processed via tailor-made compartmental toxicokinetic models. The results in broiler chickens indicate that DON3G is not hydrolysed to DON in vivo. Furthermore, the absolute oral bioavailability of DON3G in broiler chickens was low (3.79 {\textpm} 2.68 \%) and comparable to that of DON (5.56 {\textpm} 2.05 \%). After PO DON3G administration to pigs, only DON was detected in plasma, indicating a complete presystemic hydrolysis of the absorbed fraction of DON3G. However, the absorbed fraction of DON3G, recovered as DON, was approximately 5 times lower than after PO DON administration, 16.1 {\textpm} 5.4 compared with 81.3 {\textpm} 17.4 \%. Analysis of phase II metabolites revealed that biotransformation of DON and DON3G in pigs mainly consists of glucuronidation, whereas in chickens predominantly conjugation with sulphate occurred. The extent of phase II metabolism is notably higher for chickens than for pigs, which might explain the differences in sensitivity of these species to DON. Although in vitro studies demonstrate a decreased toxicity of DON3G compared with DON, the species-dependent toxicokinetic data and in vivo hydrolysis to DON illustrate the toxicological relevance and consequently the need for further research to establish a tolerable daily intake.},
  author       = {Broekaert, Nathan and Devreese, Mathias and van Bergen, Thomas and Schauvliege, Stijn and De Boevre, Marthe and De Saeger, Sarah and Vanhaecke, Lynn and Berthiller, Franz and Michlmayr, Herbert and Malachov{\'a}, Alexandra and Adam, Gerhard and Vermeulen, An and Croubels, Siska},
  issn         = {0340-5761},
  journal      = {ARCHIVES OF TOXICOLOGY},
  keyword      = {Masked mycotoxins,Modified mycotoxins,Animal trials,Fusarium toxins,MASKED MYCOTOXIN DEOXYNIVALENOL-3-GLUCOSIDE,UDP-GLUCOSYLTRANSFERASE,MASS-SPECTROMETRY,VITRO DIGESTION,T-2 TOXIN,METABOLISM,GUT,ZEARALENONE,ABSORPTION,EXCRETION},
  language     = {eng},
  number       = {2},
  pages        = {699--712},
  title        = {In vivo contribution of deoxynivalenol-3-\ensuremath{\beta}-D-glucoside to deoxynivalenol exposure in broiler chickens and pigs: oral bioavailability, hydrolysis and toxicokinetics},
  url          = {http://dx.doi.org/10.1007/s00204-016-1710-2},
  volume       = {91},
  year         = {2017},
}

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