Deoxynivalenol-3-β-D-glucoside : in vitro cytotoxicity and in vivo oral bioavailability and hydrolysis in broiler chicken and pig

In addition to DON, cereals are often co-contaminated with modified forms of DON, such as deoxynivalenol-3-β-D-glucoside (DON3G), 3-acetyl-deoxynivalenol (3ADON) or 15-acetyl-deoxynivalenol (15ADON). Due to the lack of information on toxicity and bioavailability of modified mycotoxins, current risk assessment assumes that these modified forms are equally toxic to their respective unmodified counterparts. The goal of the in vitro study was to determine the intrinsic cytotoxicity of modified DON forms towards porcine intestinal epithelial cells by means of a flow cytometric technique. Quantification of viable cells, apoptotic and necrotic cells indicate following toxicity ranking: DON3G << 3ADON < DON ≈ 15ADON. For the in vivo part, cross-over animal trials were performed with intravenous and oral administration of DON3G and DON to broiler chickens and pigs. Systemic and portal plasma concentrations of DON and DON3G 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. 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 oral DON3G administration to pigs, only DON was detected in plasma, indicating a complete presystemic hydrolysis. However, the absorbed fraction of DON3G, recovered as DON, was approximately 5 times lower than after oral DON administration, 16.1±5.4% compared to 81.3±17.4%. Additionally, analysis of phase II metabolites revealed that biotransformation of DON in pigs mainly consists of limited glucuronidation, whereas in chickens extensive conjugation with sulfate occurs, these observations might explain the differences in sensitivity of these species to DON. Although in vitro studies demonstrate a decreased toxicity of DON3G compared to DON, the species dependent toxicokinetic data and in vivo hydrolysis to DON illustrate the toxicological relevance of DON3G.

Jaar van publicatie:2016