Document Detail


Intracellular zinc stores protect the intestinal epithelium from Ochratoxin A toxicity.
MedLine Citation:
PMID:  19720134     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Ochratoxin A (OTA) is a harmful mycotoxin frequently contaminating foods, feeds and beverages. OTA was reported to be nephrotoxic, immunotoxic, hepatotoxic and a potential carcinogen, with yet poorly characterized mechanisms. Although intestinal cells are relatively resistant to high concentrations of OTA, interaction with other dietary factors or specific nutritional conditions may increase OTA toxicity to the intestinal mucosa. The role of intracellular zinc stores in protecting the integrity of intestinal mucosa has been investigated in human Caco-2/TC7 cells challenged with OTA. Zinc depletion of cells incubated with TPEN, a specific zinc chelator, caused an increase of tight junction permeability in OTA treated cells, accompanied by increased apoptosis. These effects were fully reverted by zinc supplementation during TPEN treatment, showing a specific role for this micronutrient in enterocyte defence mechanisms from OTA toxicity. A complex perturbation of zinc homeostasis was also demonstrated by analyzing the expression of genes coding for proteins involved in cellular zinc. In particular, zinc-dependent up-regulation of the metallothionein gene MT2A upon OTA treatment may indicate that the mycotoxin acts through generation of redox imbalance and that zinc deprivation reduces the intracellular defence mechanisms against noxious insults.
Authors:
G Ranaldi; V Caprini; Y Sambuy; G Perozzi; C Murgia
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-08-29
Journal Detail:
Title:  Toxicology in vitro : an international journal published in association with BIBRA     Volume:  23     ISSN:  1879-3177     ISO Abbreviation:  Toxicol In Vitro     Publication Date:  2009 Dec 
Date Detail:
Created Date:  2009-11-13     Completed Date:  2010-01-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8712158     Medline TA:  Toxicol In Vitro     Country:  England    
Other Details:
Languages:  eng     Pagination:  1516-21     Citation Subset:  IM    
Affiliation:
National Research Institute on Food and Nutrition (INRAN), Via Ardeatina 546, 00178 Rome, Italy. ranaldi@inran.it
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MeSH Terms
Descriptor/Qualifier:
Caco-2 Cells
Cation Transport Proteins / genetics,  physiology
Electric Impedance
Ethylamines / pharmacology
Humans
Intestinal Mucosa / drug effects*
Metallothionein / genetics
Ochratoxins / toxicity*
Pyridines / pharmacology
Zinc / physiology*
Chemical
Reg. No./Substance:
0/Cation Transport Proteins; 0/Ethylamines; 0/MT2A protein, human; 0/N,N,N',N'-tetrakis(2-pyridylmethyl)ethane-1,2-diamine; 0/Ochratoxins; 0/Pyridines; 0/SLC30A1 protein, human; 0/SLC39A7 protein, human; 303-47-9/ochratoxin A; 7440-66-6/Zinc; 9038-94-2/Metallothionein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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