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Archives of Toxicology

, Volume 91, Issue 2, pp 699–712 | Cite as

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

  • Nathan Broekaert
  • Mathias Devreese
  • Thomas van Bergen
  • Stijn Schauvliege
  • Marthe De Boevre
  • Sarah De Saeger
  • Lynn Vanhaecke
  • Franz Berthiller
  • Herbert Michlmayr
  • Alexandra Malachová
  • Gerhard Adam
  • An Vermeulen
  • Siska CroubelsEmail author
Toxicokinetics and Metabolism

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

Modified mycotoxins Masked mycotoxins Fusarium toxins Animal trials 

Notes

Acknowledgments

This research was funded by a Ghent University Special Research Fund grant (No. I/00105/01). The authors also acknowledge funding from the Vienna Science and Technology Fund (WWTF LS12-012), the Austrian Science Fund (FWF) (SFB F3708), the Austrian Federal Ministry of Science, Research and Economy and the Austrian National Foundation of Research, Technology and Development. Furthermore, the authors are grateful towards Gunther Antonissen, Sophie Fraeyman, Thomas De Mil, Anneleen Watteyn, Elke Gasthuys, Joske Millecam, Joren De Smet, Julie Muyle and Marlien Schaeck for the experienced assistance during the animal trials.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Nathan Broekaert
    • 1
  • Mathias Devreese
    • 2
  • Thomas van Bergen
    • 2
  • Stijn Schauvliege
    • 2
  • Marthe De Boevre
    • 3
  • Sarah De Saeger
    • 3
  • Lynn Vanhaecke
    • 4
  • Franz Berthiller
    • 5
  • Herbert Michlmayr
    • 6
  • Alexandra Malachová
    • 5
  • Gerhard Adam
    • 6
  • An Vermeulen
    • 3
  • Siska Croubels
    • 1
    Email author
  1. 1.Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
  2. 2.Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
  3. 3.Department of Bioanalysis, Faculty of Pharmaceutical SciencesGhent UniversityGhentBelgium
  4. 4.Department of Veterinary Public Health and Food Safety, Faculty of Veterinary MedicineGhent UniversityMerelbekeBelgium
  5. 5.Christian Doppler Laboratory for Mycotoxin-Metabolism, Department IFA-TullnUniversity of Natural Resources and Life Sciences, ViennaViennaAustria
  6. 6.Department of Applied Genetics and Cell BiologyUniversity of Natural Resources and Life Sciences, ViennaViennaAustria

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