Document Detail


Toxicity of deoxynivalenol and its acetylated derivatives on the intestine: differential effects on morphology, barrier function, tight junctions proteins and MAPKinases.
MedLine Citation:
PMID:  22859312     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The intestinal epithelium is the first barrier against food contaminants and is highly sensitive to mycotoxins, especially deoxynivalenol (DON). Consumption of DON-contaminated food is associated with outbreaks of gastroenteritis. In cereals and their by-products, DON is present together with two acetylated derivatives, 3-ADON and 15-ADON. Here, we compared the intestinal toxicity of DON and A-DONs, using non cytotoxic doses. The toxicity was assessed using in vitro (intestinal epithelial cell line), ex vivo (intestinal explants) and in vivo (animals exposed to mycotoxin-contaminated diets) models. The effects were studied on cell proliferation, barrier function and intestinal structure. The mechanism of toxicity was investigated by measuring the expression of the tight-junction proteins and of phosphorylated ERK1/2, p38 and JNK, effectors of signaling pathway involved in cellular programs including embryogenesis, proliferation, differentiation and apoptosis. On proliferating cells, 3-ADON was less toxic than DON, which was less toxic than 15-ADON. On differentiated cells, 15-ADON impaired the barrier function whereas DON and 3-ADON did not have a significant effect. Similarly, ex vivo and in vivo, 15-ADON caused more histological lesions than DON or 3-ADON. At the molecular level, the 15-ADON activated the MAPK ERK1/2, p38 and JNK, both in the intestinal cell line, explants and the jejunum from exposed animals at lower dose than DON and 3-ADON. Our results show that the higher toxicity of 15-DON is due to its ability to activate the MAPK. Given that cereal-based foods are contaminated with DON and acetylated-DON, the higher toxicity of 15-ADON should be taken into account.
Authors:
Philippe Pinton; Dima Tsybulskyy; Joelma Lucioli; Joëlle Laffitte; Patrick Callu; Faouzi Lyazhri; François Grosjean; Ana-Paula Bracarense; Martine Kolf-Clauw; Isabelle P Oswald
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-2
Journal Detail:
Title:  Toxicological sciences : an official journal of the Society of Toxicology     Volume:  -     ISSN:  1096-0929     ISO Abbreviation:  Toxicol. Sci.     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9805461     Medline TA:  Toxicol Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
INRA, UMR1331, Toxalim, Research Centre in Food Toxicology, F-31027 Toulouse, France.
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