Emesis to trichothecene deoxynivalenol and its congeners correspond to secretion of peptide YY and 5-HT.

The type B trichothecenes pollute food crops and have been associated to alimentary toxicosis resulted in emetic reaction in human and animal. This group of mycotoxins consists deoxynivalenol (DON) and four structurally related congeners: 3-acetyl-deoxynivalenol (3-ADON), 15-acetyl deoxynivalenol (15-ADON), nivalenol (NIV) and 4-acetyl-nivalenol (fusarenon X, FX). While emesis induced by intraperitoneally dosed to DON in the mink has been related to plasma up-grading of 5-hydroxytryptamine (5-HT) and neurotransmitters peptide YY (PYY), the impact of oral dosing with DON or its four congeners on secretion of these chemical substances have not been established. The aim of this work was to contraste emetic influence to type B trichothecene mycotoxins by orally dosing and involve these influence to PYY and 5-HT. All five toxins attracted marked emetic reaction that are relevant to elevated PYY and 5-HT. The reduction in vomiting induced by the five toxins and PYY was due to blocking of the neuropeptide Y2 receptor. The inhibition of the induced vomiting response by 5-HT and all five toxins is regulated by the 5-HT3 receptor inhibitor granisetron. In a word, our results indicate that PYY and 5-HT take a key role in the emetic reaction evoked by type B trichothecenes.

Enterocyte-Based Bioassay via Quantitative Combination of Proinflammatory Sentinels Specific to 8-keto-trichothecenes.

Type B 8-keto-trichothecenes are muco-active mycotoxins that exist as inevitable contaminants in cereal-based foodstuffs. Gut-associated inflammation is an early frontline response during human and animal exposure to these mycotoxins. Despite various tools for chemical identification, optimized biomonitoring of sentinel response-associated biomarkers is required to assess the specific proinflammatory actions of 8-keto-trichothecenes in the gut epithelial barrier. In the present study, intoxication with 8-keto-trichothecenes in human intestinal epithelial cells was found to trigger early response gene 1 product (EGR-1) that plays crucial roles in proinflammatory chemokine induction. In contrast, epithelial exposure to 8-keto-trichothecenes resulted in downregulated expression of nuclear factor NF-kappa-B p65 protein, a key transcription factor, during general inflammatory responses in the gut. Based on the early molecular patterns of expression, the inflammation-inducing activity of 8-keto-trichothecenes was quantified using intestinal epithelial cells with dual reporters for EGR-1 and p65 proteins. EGR-1-responsive elements were linked to luciferase reporter while p65 promoter was bound to secretory alkaline phosphatase (SEAP) reporter. In response to conventional inflammagens such as endotoxins and cytokines such as TNF-α, both luciferase and SEAP activity were elevated in a dose-dependent manner. However, as expected from the mechanistic evaluation, 8-keto-trichothecene-exposed dual reporters of luciferase and SEAP displayed contrasting expression patterns. Furthermore, 8-keto-trichothecene-elevated EGR-1-responsive luciferase activity was improved by deficiency of PSMA3, an α-type subunit of the 20S proteasome core complex for ubiquitin-dependent EGR-1 degradation. This molecular event-based dual biomonitoring in epithelial cells is a promising supplementary tool for detecting typical molecular inflammatory pathways in response to 8-keto-trichothecenes in the food matrix.