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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MDPI AG
2016-07-01
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| Series: | Toxins |
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| Online Access: | http://www.mdpi.com/2072-6651/8/8/232 |
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| author | El Hassan Ajandouz Stéphane Berdah Vincent Moutardier Thierry Bege David Jérémie Birnbaum Josette Perrier Eric Di Pasquale Marc Maresca |
| author_facet | El Hassan Ajandouz Stéphane Berdah Vincent Moutardier Thierry Bege David Jérémie Birnbaum Josette Perrier Eric Di Pasquale Marc Maresca |
| author_sort | El Hassan Ajandouz |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-12T05:45:47Z |
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| id | doaj.art-e45e812b86564d97ab72a200c4e6df3b |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-04-12T05:45:47Z |
| publishDate | 2016-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-e45e812b86564d97ab72a200c4e6df3b2022-12-22T03:45:27ZengMDPI AGToxins2072-66512016-07-018823210.3390/toxins8080232toxins8080232Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo ApproachesEl Hassan Ajandouz0Stéphane Berdah1Vincent Moutardier2Thierry Bege3David Jérémie Birnbaum4Josette Perrier5Eric Di Pasquale6Marc Maresca7Aix Marseille Univ, CNRS, Centrale Marseille, iSm2, Marseille, FranceAix Marseille Univ, Laboratoire de Biomécanique Appliquée, UMRT24 IFSTTAR, Faculté de médecine secteur Nord, Boulevard Pierre Dramard, F-13916 Marseille Cedex 20, FranceAix Marseille Univ, Laboratoire de Biomécanique Appliquée, UMRT24 IFSTTAR, Faculté de médecine secteur Nord, Boulevard Pierre Dramard, F-13916 Marseille Cedex 20, FranceAix Marseille Univ, Laboratoire de Biomécanique Appliquée, UMRT24 IFSTTAR, Faculté de médecine secteur Nord, Boulevard Pierre Dramard, F-13916 Marseille Cedex 20, FranceAix Marseille Univ, Laboratoire de Biomécanique Appliquée, UMRT24 IFSTTAR, Faculté de médecine secteur Nord, Boulevard Pierre Dramard, F-13916 Marseille Cedex 20, FranceAix Marseille Univ, CNRS, Centrale Marseille, iSm2, Marseille, FranceAix Marseille Univ, CNRS, CRN2M, Marseille, France & CSO@MyEnterix, Marseille, FranceAix Marseille Univ, CNRS, Centrale Marseille, iSm2, Marseille, FranceIn 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.http://www.mdpi.com/2072-6651/8/8/232mycotoxindeoxynivalenol3-acetyldeoxynivalenol15-acetyldeoxynivalenolcarboxylesterasehuman explantsCaco-2T84HepG2A498 |
| spellingShingle | El Hassan Ajandouz Stéphane Berdah Vincent Moutardier Thierry Bege David Jérémie Birnbaum Josette Perrier Eric Di Pasquale Marc Maresca Hydrolytic Fate of 3/15-Acetyldeoxynivalenol in Humans: Specific Deacetylation by the Small Intestine and Liver Revealed Using in Vitro and ex Vivo Approaches Toxins mycotoxin deoxynivalenol 3-acetyldeoxynivalenol 15-acetyldeoxynivalenol carboxylesterase human explants Caco-2 T84 HepG2 A498 |
| 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 | mycotoxin deoxynivalenol 3-acetyldeoxynivalenol 15-acetyldeoxynivalenol carboxylesterase human explants Caco-2 T84 HepG2 A498 |
| url | http://www.mdpi.com/2072-6651/8/8/232 |
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