In vivo contribution of deoxynivalenol-3-β-D-glucoside to deoxynivalenol exposure in broiler chickens and pigs: oral bioavailability, hydrolysis and toxicokinetics.
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.
Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
Nathan
N
Broekaert
Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
Mathias
M
Devreese
Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
Thomas
T
van Bergen
Department of Surgery and Anaesthesiology of Domestic Animals, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
Stijn
S
Schauvliege
Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
Marthe
M
De Boevre
Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
Sarah
S
De Saeger
Department of Veterinary Public Health and Food Safety, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
Lynn
L
Vanhaecke
Christian Doppler Laboratory for Mycotoxin-Metabolism, Department IFA-Tulln, University of Natural Resources and Life Sciences, Vienna, Konrad-Lorenz-Str. 20, 3430, Vienna, Tulln, Austria.
Franz
F
Berthiller
Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Konrad-Lorenz-Str. 24, 3430, Vienna, Tulln, Austria.
Herbert
H
Michlmayr
Christian Doppler Laboratory for Mycotoxin-Metabolism, Department IFA-Tulln, University of Natural Resources and Life Sciences, Vienna, Konrad-Lorenz-Str. 20, 3430, Vienna, Tulln, Austria.
Alexandra
A
Malachová
Department of Applied Genetics and Cell Biology, University of Natural Resources and Life Sciences, Vienna, Konrad-Lorenz-Str. 24, 3430, Vienna, Tulln, Austria.
Gerhard
G
Adam
Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, 9000, Ghent, Belgium.
An
A
Vermeulen
Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. siska.croubels@ugent.be.
Siska
S
Croubels
D061605:Administration, Intravenous; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002645:Chickens; D002853:Chromatography, Liquid / Q000379:methods; D005960:Glucosides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D006868:Hydrolysis; D008297:Male; D015203:Reproducibility of Results; D034421:Sus scrofa; D053719:Tandem Mass Spectrometry / Q000379:methods; D066007:Toxicokinetics; D014255:Trichothecenes / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity
D005960:Glucosides; D014255:Trichothecenes; C542050:deoxynivalenol-3-glucoside; C007262:deoxynivalenol
Animal trials; Fusarium toxins; Masked mycotoxins; Modified mycotoxins