Oral Bioavailability, Hydrolysis, and Comparative Toxicokinetics of 3-Acetyldeoxynivalenol and 15-Acetyldeoxynivalenol in Broiler Chickens and Pigs

Abstract

The goal of this study was to determine the absolute oral bioavailability, (presystemic) hydrolysis and toxicokinetic characteristics of deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol in broiler chickens and pigs. Crossover animal trials were performed with intravenous and oral administration of deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol to broilers and pigs. Plasma concentrations were analyzed by using liquid chromatography-tandem mass spectrometry, and data were processed via a tailor-made compartmental toxicokinetic analysis. The results in broiler chickens showed that the absorbed fraction after oral deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol administration was 10.6, 18.2, and 42.2%, respectively. This fraction was completely hydrolyzed presystemically for 3-acetyldeoxynivalenol to deoxynivalenol and to a lesser extent (75.4%) for 15-acetyldeoxynivalenol. In pigs, the absorbed fractions were 100% for deoxynivalenol, 3-acetyldeoxynivalenol, and 15-acetyldeoxynivalenol, and both 3-acetyldeoxynivalenol and 15-acetyldeoxynivalenol were completely hydrolyzed presystemically. The disposition properties of 3-acetyldeoxynivalenol and 15-acetyldeoxynivalenol demonstrate their toxicological relevance and consequently the possible need to establish a tolerable daily intake.

Modeling the emetic potencies of food-borne trichothecenes by benchmark dose methodology

“…In pigs, the rapid and nearly complete pre-systemic hydrolysis (99%) of 15-ADON to DON was observed. However, the rates of clearance were in increasing order: 3-ADON > 15-ADON > DON (Broekaert et al, 2015). Although both 3-ADON and 15-ADON ultimately undergo hydrolysis in the intestine before absorption, each toxin (DON, 3-ADON, and 15-ADON) exerts a different toxicity on the local tissue (Broekaert et al, 2015).…”

“…However, the rates of clearance were in increasing order: 3-ADON > 15-ADON > DON (Broekaert et al, 2015). Although both 3-ADON and 15-ADON ultimately undergo hydrolysis in the intestine before absorption, each toxin (DON, 3-ADON, and 15-ADON) exerts a different toxicity on the local tissue (Broekaert et al, 2015). For example, Pinton et al (2012) used in vitro, ex vivo and in vivo studies to compare the effects of DON, 3-ADON and 15-ADON on the barrier function of intestinal cells and activation of MAPK.…”

“…In contrast to a number of previous studies that indicated that acetylation of DON at C-15 to 15-ADON increases cytotoxicity (Desjardins et al, 2007), this study showed that the emetic potency of DON was greater than 15-ADON. The low toxicity of 15-ADON in vivo could be partly due to deacetylation to DON in the intestine prior to absorption (Veršilovskis et al, 2012) and in part, attributed to faster rates of clearance as compared to DON (Broekaert et al, 2015). In pigs, the rapid and nearly complete pre-systemic hydrolysis (99%) of 15-ADON to DON was observed.…”

Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches

“…3/15ADON (Figure 1) are precursors in the synthesis of DON [20] and are thus found in food as a mixture with DON. Indeed, like DON, 3/15ADON have a high prevalence in cereals (87% and 73% of positive samples for 3ADON and 15ADON, respectively) with contamination levels ranging from 300 to 1000 μg/kg leading to daily exposure of animals and humans to 3/15ADON [21,22,23]. Although in vivo and in vitro experiments have demonstrated that 3/15ADON could be absorbed by the intestinal epithelium, oral exposures of chickens, rats and pigs to 3/15ADON only result in DON and/or detoxification products of DON (i.e., the 3/15-glucuronic acid conjugates of DON and the de-epoxide form of DON, i.e., DOM-1) being present in their blood suggesting a pre-systemic and/or systemic deacetylation [21,24,25,26,27,28].…”

“…Broekaert et al [21] elegantly showed that both oral and intravenous (i.v) exposures of pigs to 3- or 15ADON resulted in their complete transformation into DON, demonstrating that pre-systemic and systemic deacetylation may occur in parallel. Interestingly, the authors also demonstrated that traces of 15ADON are present in the blood of chickens after oral or i.v treatment, suggesting that, at least in chickens, contrarily to 3ADON, 15ADON may partially resist deacetylation [21].…”