Document Detail


The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction.
MedLine Citation:
PMID:  20167873     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Disruption of the intestinal barrier is a causal factor in the development of alcoholic endotoxemia and hepatitis. This study was undertaken to determine whether zinc deficiency is related to the deleterious effects of alcohol on the intestinal barrier. Mice were pair fed an alcohol or isocaloric liquid diet for 4 wk, and hepatitis was detected in association with elevated blood endotoxin level. Alcohol exposure significantly increased the permeability of the ileum but did not affect the barrier function of the duodenum or jejunum. Reduction of tight-junction proteins at the ileal epithelium was detected in alcohol-fed mice although alcohol exposure did not cause apparent histopathological changes. Alcohol exposure significantly reduced the ileal zinc concentration in association with accumulation of reactive oxygen species. Caco-2 cell culture demonstrated that alcohol exposure increases the intracellular free zinc because of oxidative stress. Zinc deprivation caused epithelial barrier disruption in association with disassembling of tight junction proteins in the Caco-2 monolayer cells. Furthermore, minor zinc deprivation exaggerated the deleterious effect of alcohol on the epithelial barrier. In conclusion, epithelial barrier dysfunction in the distal small intestine plays an important role in alcohol-induced gut leakiness, and zinc deficiency attributable to oxidative stress may interfere with the intestinal barrier function by a direct action on tight junction proteins or by sensitizing to the effects of alcohol.
Authors:
Wei Zhong; Craig J McClain; Matthew Cave; Y James Kang; Zhanxiang Zhou
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-18
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  298     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-20     Completed Date:  2010-05-06     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G625-33     Citation Subset:  IM    
Affiliation:
China Agricultural University, Beijing, China.
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MeSH Terms
Descriptor/Qualifier:
Alcohol Drinking / physiopathology*
Animals
Caco-2 Cells
Ethanol / pharmacology
Humans
Ileum / physiology*
Intestines / drug effects*
Liver Diseases, Alcoholic / pathology,  physiopathology
Male
Mice
Mice, Inbred C57BL
Oxidative Stress
Permeability / drug effects
Reactive Oxygen Species / metabolism
Tight Junctions / metabolism
Zinc / deficiency*
Grant Support
ID/Acronym/Agency:
K23 AA018399-02/AA/NIAAA NIH HHS; K23 AA018399-03/AA/NIAAA NIH HHS; R01 AA018016-04/AA/NIAAA NIH HHS; R01 AA018869-03/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Reactive Oxygen Species; 64-17-5/Ethanol; 7440-66-6/Zinc
Comments/Corrections

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


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