The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction
Open accessAbstract
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.
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Binge alcohol exposure promotes gut leakiness.
“binge alcohol exposure [232], [233], [234], [235], [236], [237], [238], [239] and nonalcoholic substances including fructose [240], [241], [242] are known to promote gut leakiness, contributing to more severe inflammatory liver disease.”
Gut leakiness contributes to more severe inflammatory liver disease.
“binge alcohol exposure [232], [233], [234], [235], [236], [237], [238], [239] and nonalcoholic substances including fructose [240], [241], [242] are known to promote gut leakiness, contributing to more severe inflammatory liver disease.”
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- Authors
- Zhong, W., McClain, C. J., Cave, M., Kang, Y. J., & Zhou, Z.
- Affiliations
- China Agricultural University (CN)
- University of Louisville (US)
- Corresponding author
- Zhou, Zhanxiang
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2010-05
- Volume
- 298
- Issue
- 5
- Pages
- G625-G633
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- PMC
- PMC2867425
- OpenAlex
- W2140449647
- Cited by
- 214
- References
- 50
- Citations by year
- 2026: 5 · 2025: 14 · 2024: 13 · 2023: 17 · 2022: 12 · 2021: 12 · 2020: 15 · 2019: 12 · 2018: 7 · 2017: 13 · 2016: 7 · 2015: 24 · 2014: 19 · 2013: 16 · 2012: 16
- FWCI
- 9.53
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA018016, K23AA018399, R01AA018869, R01AA014623)
- National Institute of Environmental Health Sciences (R01ES021375)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Keywords
- zinc deficiency, alcohol, intestinal barrier dysfunction, tight junction proteins, intestinal permeability, ileum, oxidative stress, reactive oxygen species, endotoxemia, alcoholic hepatitis, leaky gut, Caco-2 cells
- MeSH terms
- Alcohol Drinking, Ethanol, Animals, Humans, Ileum, Intestines, Liver Diseases, Alcoholic, Male, Mice, Inbred C57BL, Permeability, Zinc, Reactive Oxygen Species, Oxidative Stress, Caco-2 Cells, Tight Junctions, Mice
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