The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction.
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.
Zhong
Wei
W
China Agricultural University, Beijing, China.
McClain
Craig J
CJ
Cave
Matthew
M
Kang
Y James
YJ
Zhou
Zhanxiang
Z
D000428:Alcohol Drinking / Q000503:physiopathology*; D000818:Animals; D018938:Caco-2 Cells; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D007082:Ileum / Q000502:physiology*; D007422:Intestines / Q000187:drug effects*; D008108:Liver Diseases, Alcoholic / Q000473:pathology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D010539:Permeability / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D019108:Tight Junctions / Q000378:metabolism; D015032:Zinc / Q000172:deficiency*
D017382:Reactive Oxygen Species; D000431:Ethanol; D015032:Zinc