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

In addition to deoxynivalenol (DON), acetylated derivatives, i.e., 3-acetyl and 15-acetyldexynivalenol (or 3/15ADON), are present in cereals leading to exposure to these mycotoxins. Animal and human studies suggest that 3/15ADON are converted into DON after their ingestion through hydrolysis of the...

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Autores principales: Ajandouz, El Hassan, Berdah, Stéphane, Moutardier, Vincent, Bege, Thierry, Birnbaum, David Jérémie, Perrier, Josette, Di Pasquale, Eric, Maresca, Marc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999848/
https://www.ncbi.nlm.nih.gov/pubmed/27483321
http://dx.doi.org/10.3390/toxins8080232
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author Ajandouz, El Hassan
Berdah, Stéphane
Moutardier, Vincent
Bege, Thierry
Birnbaum, David Jérémie
Perrier, Josette
Di Pasquale, Eric
Maresca, Marc
author_facet Ajandouz, El Hassan
Berdah, Stéphane
Moutardier, Vincent
Bege, Thierry
Birnbaum, David Jérémie
Perrier, Josette
Di Pasquale, Eric
Maresca, Marc
author_sort Ajandouz, El Hassan
collection PubMed
description In addition to deoxynivalenol (DON), acetylated derivatives, i.e., 3-acetyl and 15-acetyldexynivalenol (or 3/15ADON), are present in cereals leading to exposure to these mycotoxins. Animal and human studies suggest that 3/15ADON are converted into DON after their ingestion through hydrolysis of the acetyl moiety, the site(s) of such deacetylation being still uncharacterized. We used in vitro and ex vivo approaches to study the deacetylation of 3/15ADON by enzymes and cells/tissues present on their way from the food matrix to the blood in humans. We found that luminal deacetylation by digestive enzymes and bacteria is limited. Using human cells, tissues and S9 fractions, we were able to demonstrate that small intestine and liver possess strong deacetylation capacity compared to colon and kidneys. Interestingly, in most cases, deacetylation was more efficient for 3ADON than 15ADON. Although we initially thought that carboxylesterases (CES) could be responsible for the deacetylation of 3/15ADON, the use of pure human CES1/2 and of CES inhibitor demonstrated that CES are not involved. Taken together, our original model system allowed us to identify the small intestine and the liver as the main site of deacetylation of ingested 3/15ADON in humans.
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spelling pubmed-49998482016-09-01 Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches Ajandouz, El Hassan Berdah, Stéphane Moutardier, Vincent Bege, Thierry Birnbaum, David Jérémie Perrier, Josette Di Pasquale, Eric Maresca, Marc Toxins (Basel) Article In addition to deoxynivalenol (DON), acetylated derivatives, i.e., 3-acetyl and 15-acetyldexynivalenol (or 3/15ADON), are present in cereals leading to exposure to these mycotoxins. Animal and human studies suggest that 3/15ADON are converted into DON after their ingestion through hydrolysis of the acetyl moiety, the site(s) of such deacetylation being still uncharacterized. We used in vitro and ex vivo approaches to study the deacetylation of 3/15ADON by enzymes and cells/tissues present on their way from the food matrix to the blood in humans. We found that luminal deacetylation by digestive enzymes and bacteria is limited. Using human cells, tissues and S9 fractions, we were able to demonstrate that small intestine and liver possess strong deacetylation capacity compared to colon and kidneys. Interestingly, in most cases, deacetylation was more efficient for 3ADON than 15ADON. Although we initially thought that carboxylesterases (CES) could be responsible for the deacetylation of 3/15ADON, the use of pure human CES1/2 and of CES inhibitor demonstrated that CES are not involved. Taken together, our original model system allowed us to identify the small intestine and the liver as the main site of deacetylation of ingested 3/15ADON in humans. MDPI 2016-07-28 /pmc/articles/PMC4999848/ /pubmed/27483321 http://dx.doi.org/10.3390/toxins8080232 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ajandouz, El Hassan
Berdah, Stéphane
Moutardier, Vincent
Bege, Thierry
Birnbaum, David Jérémie
Perrier, Josette
Di Pasquale, Eric
Maresca, Marc
Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches
title Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches
title_full Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches
title_fullStr Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches
title_full_unstemmed Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches
title_short Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches
title_sort hydrolytic fate of 3/15-acetyldeoxynivalenol in humans: specific deacetylation by the small intestine and liver revealed using in vitro and ex vivo approaches
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999848/
https://www.ncbi.nlm.nih.gov/pubmed/27483321
http://dx.doi.org/10.3390/toxins8080232
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