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.
abstract: 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.
authors.affiliation: Aix Marseille Univ, CNRS, Centrale Marseille, iSm2, Marseille, France. el-hassan.ajandouz@univ-amu.fr.
authors.forename: El Hassan
authors.initials: el H
authors.lastname: Ajandouz
authors.affiliation: Aix Marseille Univ, Laboratoire de Biom&#233;canique Appliqu&#233;e, UMRT24 IFSTTAR, Facult&#233; de m&#233;decine secteur Nord, Boulevard Pierre Dramard, F-13916 Marseille Cedex 20, France. stephane.berdah@ap-hm.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Berdah
authors.affiliation: Aix Marseille Univ, Laboratoire de Biom&#233;canique Appliqu&#233;e, UMRT24 IFSTTAR, Facult&#233; de m&#233;decine secteur Nord, Boulevard Pierre Dramard, F-13916 Marseille Cedex 20, France. vincent.moutardier@univ-amu.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Moutardier
authors.affiliation: Aix Marseille Univ, Laboratoire de Biom&#233;canique Appliqu&#233;e, UMRT24 IFSTTAR, Facult&#233; de m&#233;decine secteur Nord, Boulevard Pierre Dramard, F-13916 Marseille Cedex 20, France. thierry.bege@ap-hm.fr.
authors.forename: Thierry
authors.initials: T
authors.lastname: Bege
authors.affiliation: Aix Marseille Univ, Laboratoire de Biom&#233;canique Appliqu&#233;e, UMRT24 IFSTTAR, Facult&#233; de m&#233;decine secteur Nord, Boulevard Pierre Dramard, F-13916 Marseille Cedex 20, France. david.birnbaum@ap-hm.fr.
authors.forename: David Jérémie
authors.initials: DJ
authors.lastname: Birnbaum
authors.affiliation: Aix Marseille Univ, CNRS, Centrale Marseille, iSm2, Marseille, France. josette.perrier@univ-amu.fr.
authors.forename: Josette
authors.initials: J
authors.lastname: Perrier
authors.affiliation: Aix Marseille Univ, CNRS, CRN2M, Marseille, France &amp; CSO@MyEnterix, Marseille, France. eric.di-pasquale@myenterix.com.
authors.forename: Eric
authors.initials: E
authors.lastname: Di Pasquale
authors.affiliation: Aix Marseille Univ, CNRS, Centrale Marseille, iSm2, Marseille, France. m.maresca@univ-amu.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Maresca
mesh_terms: D000107:Acetylation; D000328:Adult; D000368:Aged; D001419:Bacteria / Q000201:enzymology; D018938:Caco-2 Cells; D043182:Carboxylesterase / Q000378:metabolism; D003106:Colon / Q000201:enzymology / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D056945:Hep G2 Cells; D006801:Humans; D006868:Hydrolysis; D007421:Intestine, Small / Q000201:enzymology* / Q000382:microbiology; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014255:Trichothecenes / Q000378:metabolism*
chemical_list: D014255:Trichothecenes; C043247:3-acetyldeoxynivalenol; C046760:15-acetyldeoxynivalenol; D043182:Carboxylesterase; C007262:deoxynivalenol
keywords: 15-acetyldeoxynivalenol; 3-acetyldeoxynivalenol; A498; Caco-2; HepG2; T84; carboxylesterase; deoxynivalenol; human explants; mycotoxin