title: Deoxynivalenol and Its Modified Forms: Are There Major Differences?
abstract: Considering the diverse toxic effects of theFusariumtoxin deoxynivalenol (DON), its common occurrence in wheat-based products, and its stability during processing, DON constitutes an increasing health concern for humans and animals. In addition to the parent compound DON, human and animal exposure encompasses the acetylated fungal metabolites 3-acetyl-deoxynivalenol (3ADON) and 15-acetyl-deoxynivalenol (15ADON) as well as the plant-derived DON-glucoside (DON3G) and the bacterial product de-epoxy-DON (DOM-1). In the current study we used the well-established Caco-2 cell model to compare the effects of these naturally occurring forms of DON on cell viability and markers of barrier integrity, as well as on the release of the pro-inflammatory chemokine chemokine CXC motif ligand (CXCL8). Results show that 3ADON is less potent in inducing adverse effects on barrier integrity when compared to DON, whereas 15ADON appears to be slightly more potent than DON. In contrast, DON3G and DOM-1 exerted no measurable adverse effects on the intestinal barrier. It was also demonstrated that galacto-oligosaccharides (GOS) are able to protect epithelial cells against DON and its acetylated forms, which suggests that GOS are beneficial food additives in the protection of vulnerable segments of the human population against adverse effects of DON and its derivatives.
authors.affiliation: Division of Veterinary Pharmacology, Pharmacotherapy and Toxicology, Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 104, 3584-CM Utrecht, The Netherlands. a.alizadeh@uu.nl.|Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584-CG Utrecht, The Netherlands. a.alizadeh@uu.nl.
authors.forename: Arash
authors.initials: A
authors.lastname: Alizadeh
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584-CG Utrecht, The Netherlands. s.braber@uu.nl.
authors.forename: Saskia
authors.initials: S
authors.lastname: Braber
authors.affiliation: Division of Veterinary Pharmacology, Pharmacotherapy and Toxicology, Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 104, 3584-CM Utrecht, The Netherlands. a.peyman@uu.nl.|Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584-CG Utrecht, The Netherlands. a.peyman@uu.nl.
authors.forename: Peyman
authors.initials: P
authors.lastname: Akbari
authors.affiliation: Division of Veterinary Pharmacology, Pharmacotherapy and Toxicology, Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 104, 3584-CM Utrecht, The Netherlands. a.d.kraneveld@uu.nl.|Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584-CG Utrecht, The Netherlands. a.d.kraneveld@uu.nl.
authors.forename: Aletta
authors.initials: A
authors.lastname: Kraneveld
authors.affiliation: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584-CG Utrecht, The Netherlands. j.garssen@uu.nl.|Department Immunology, Nutricia Research, Uppsalalaan 12, 3584-CT Utrecht, The Netherlands. j.garssen@uu.nl.
authors.forename: Johan
authors.initials: J
authors.lastname: Garssen
authors.affiliation: Division of Veterinary Pharmacology, Pharmacotherapy and Toxicology, Institute for Risk Assessment Sciences, Utrecht University, Yalelaan 104, 3584-CM Utrecht, The Netherlands. j.fink@uu.nl.
authors.forename: Johanna
authors.initials: J
authors.lastname: Fink-Gremmels
mesh_terms: D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009844:Oligosaccharides / Q000494:pharmacology; D014255:Trichothecenes / Q000633:toxicity*
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D009844:Oligosaccharides; D014255:Trichothecenes; D007770:L-Lactate Dehydrogenase; C007262:deoxynivalenol
keywords: 15-acetyl-deoxynivalenol; 3-acetyl-deoxynivalenol; CXCL8; DON-3-O-glucoside; de-epoxy-DON; deoxynivalenol; intestinal barrier; mycotoxin