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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 [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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“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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Cites
Parlesak, A., Schäfer, C., Schütz, T., Bode, J. C., & Bode, C. (2000) · Journal of Hepatology · doi:10.1016/s0168-8278(00)80242-1 · Cited by 647
Tight junctions and the modulation of barrier function in disease
Förster, C. Y. (2008) · Histochemistry and Cell Biology · doi:10.1007/s00418-008-0424-9 · Cited by 617
Intestinal barrier: An interface between health and disease
Farhadi, A., Banan, A., Fields, J. Z., & Keshavarzian, A. (2003) · Journal of Gastroenterology and Hepatology · doi:10.1046/j.1440-1746.2003.03032.x · Cited by 532
Kucharzik, T. F., Walsh, S. V., Chen, J. Z., Parkos, C. A., & Nusrat, A. (2001) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63051-9 · Cited by 523
Zinc: a multipurpose trace element
Stefanidou, M., Maravelias, C. T., Dona, A., & Spiliopoulou, C. (2005) · Archives of Toxicology · doi:10.1007/s00204-005-0009-5 · Cited by 475
Mitic, L. L., Itallie, C. M. V., & Anderson, J. M. (2000) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2000.279.2.g250 · Cited by 452
THE LEAKY GUT OF ALCOHOLISM: POSSIBLE ROUTE OF ENTRY FOR TOXIC COMPOUNDS
Bjarnason, I., Ward, K., & Peters, T. B. (1984) · The Lancet · doi:10.1016/s0140-6736(84)92109-3 · Cited by 432
Loss of the Tight Junction Protein ZO-1 in Dextran Sulfate Sodium Induced Colitis
Poritz, L. S., Garver, K. I., Green, C., Fitzpatrick, L. R., Ruggiero, F. M., & Koltun, W. A. (2007) · Journal of Surgical Research · doi:10.1016/j.jss.2006.07.050 · Cited by 414
Forsyth, C. B., Farhadi, A., Jakate, S. M., Tang, Y., Shaikh, M. W., & Keshavarzian, A. (2009) · Alcohol · doi:10.1016/j.alcohol.2008.12.009 · Cited by 404
Zinc Oxide Protects Cultured Enterocytes from the Damage Induced by Escherichia coli
Roselli, M., Finamore, A., Garaguso, I., Britti, M. S., & Mengheri, E. (2003) · Journal of Nutrition · doi:10.1093/jn/133.12.4077 · Cited by 391
Leaky Gut in Alcoholic Cirrhosis: A Possible Mechanism for Alcohol-Induced Liver Damage
Keshavarzian, A., HOLMES, E. W., Patel, M., Iber, F. L., Fields, J. Z., & Pethkar, S. (1999) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.1999.00797.x · Cited by 381
Keshavarzian, A., Farhadi, A., Forsyth, C. B., Rangan, J., Jakate, S. M., Shaikh, M. W., Banan, A., & Fields, J. Z. (2008) · Journal of Hepatology · doi:10.1016/j.jhep.2008.10.028 · Cited by 359
Rao, R. K., Seth, A., & Sheth, P. (2004) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00006.2004 · Cited by 340
Exacerbation of Alcoholic Liver Injury by Enteral Endotoxin in Rats
Mathurin, P., Deng, Q.-G., Keshavarzian, A., Choudhary, S., HOLMES, E. W., & Tsukamoto, H. (2000) · Hepatology · doi:10.1053/jhep.2000.19621 · Cited by 297
Tang, Y., Banan, A., Forsyth, C. B., Fields, J. Z., Lau, C. K., Zhang, L. J., & Keshavarzian, A. (2007) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2007.00584.x · Cited by 288
Ethanol modulation of intestinal epithelial tight junction barrier
Ma, T. Y., Nguyen, D., Bui, V., Nguyen, H. B., & Hoa, N. T. (1999) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1999.276.4.g965 · Cited by 261
Ferrier, L., Bérard, F., Debrauwer, L., Chabo, C., Langella, P., Bueno, L. P., & Fioramonti, J. (2006) · American Journal Of Pathology · doi:10.2353/ajpath.2006.050617 · Cited by 247
Finamore, A., Massimi, M., Devirgiliis, L. C., & Mengheri, E. (2008) · Journal of Nutrition · doi:10.1093/jn/138.9.1664 · Cited by 199
Zinc Supplementation Tightens “Leaky Gut” in Crohn’s Disease
Sturniolo, G. C., Leo, V. D., Ferronato, A., D’Odorico, A., & Renata D'Incà (2001) · Inflammatory Bowel Diseases · doi:10.1097/00054725-200105000-00003 · Cited by 193
Banan, A., Choudhary, S., Zhang, Y., Fields, J. Z., & Keshavarzian, A. (1999) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)35212-7 · Cited by 165
The differing effects of acute and chronic alcohol on gastric and intestinal permeability.
Keshavarzian, A., Fields, J. Z., Vaeth, J., & HOLMES, E. W. (1994) · PubMed · Cited by 165
Zinc and the Liver: An Active Interaction
Stamoulis, I., Kouraklis, G., & Theocharis, S. E. (2007) · Digestive Diseases and Sciences · doi:10.1007/s10620-006-9462-0 · Cited by 162
Bode, C., & Bode, J. C. (2005) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000189280.19073.28 · Cited by 158
Preventing Gut Leakiness by Oats Supplementation Ameliorates Alcohol-Induced Liver Damage in Rats
Keshavarzian, A., Choudhary, S., HOLMES, E. W., Yong, S., Banan, A., Jakate, S. M., & Fields, J. Z. (2001) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)29249-1 · Cited by 157
Lambert, J. C., Zhou, Z., Wang, L., Song, Z., McClain, C. J., & Kang, Y. J. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.047852 · Cited by 143
Self-citationBasuroy, S., Sheth, P., Mansbach, C. M., & Rao, R. K. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00464.2004 · Cited by 134
Effect of zinc supplementation on intestinal permeability in experimental colitis
Sturniolo, G. C., Fries, W., Mazzon, E., Leo, V. D., Barollo, M., & Renata D'Incà (2002) · Journal of Laboratory and Clinical Medicine · doi:10.1067/mlc.2002.123624 · Cited by 127
Zinc prevention and treatment of alcoholic liver disease
Kang, Y. J., & Zhou, Z. (2005) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2005.07.002 · Cited by 119
Self-citationZinc Fingers as Biologic Redox Switches?
Kröncke, K., & Klotz, L. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2269 · Cited by 113
Bagchi, D., Carryl, O. R., Tran, M. X., Krohn, R. L., Bagchi, D., Garg, A., Bagchi, M., Mitra, S., & STOHS, S. J. (1998) · Journal of Applied Toxicology · doi:10.1002/(sici)1099-1263(199801/02)18:1 · Cited by 104
Zinc Metabolism in Alcoholic Liver Disease
McClain, C. J., Antonow, D. R., Cohen, D. A., & Shedlofsky, S. I. (1986) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1986.tb05149.x · Cited by 96
Self-citationEnomoto, N., Takei, Y., Hirose, M., Ikejima, K., Miwa, H., Kitamura, T., & Sato, N. (2002) · Gastroenterology · doi:10.1053/gast.2002.34161 · Cited by 89
Zinc Deficiency Mediates Alcohol-Induced Alveolar Epithelial and Macrophage Dysfunction in Rats
Joshi, P. C., Mehta, A. J., Jaber, W. S., Fan, X., & Guidot, D. M. (2008) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2008-0209oc · Cited by 87
Villous damage induced by suction biopsy and by acute ethanol intake in normal human small intestine
Millan, M. S., Morris, G. P., Beck, I. T., & Henson, J. T. (1980) · Digestive Diseases and Sciences · doi:10.1007/bf01315213 · Cited by 83
Montalto, M., Cuoco, L., Ricci, R., Maggiano, N., Vecchio, F. M., & Gasbarrini, A. (2002) · Digestion · doi:10.1159/000063817 · Cited by 70
Cellular stress and intracellular zinc dyshomeostasis
Kröncke, K. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.03.008 · Cited by 69
Lambert, J. C., Zhou, Z., Wang, L., Song, Z., McClain, C. J., & Kang, Y. J. (2004) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)63756-x · Cited by 53
Self-citationTran, C. D., Howarth, G. S., Coyle, P. V., Philcox, J. C., Rofe, A. M., & Butler, R. N. (2003) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/77.5.1296 · Cited by 49
Semrad, C. E. (1999) · Current Gastroenterology Reports · doi:10.1007/s11894-999-0021-7 · Cited by 46
Ellis, R. D., Limb, G. A., Thompson, R. P. H., & Punchard, N. A. (1997) · Biochemical Society Transactions · doi:10.1042/bst025178s · Cited by 43
Functional and morphological alterations in small intestine mucosa of chronic alcoholics
Bhonchal, S., Nain, C. K., Prasad, K. K., Nada, R., Sharma, A. K., Sinha, S. K., & Singh, K. (2007) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2007.05080.x · Cited by 40
Banan, A., Zhang, L. J., Shaikh, M. W., Fields, J. Z., Farhadi, A., & Keshavarzian, A. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00146.2004 · Cited by 37
Banan, A., Farhadi, A., Fields, J. Z., Mutlu, E., Zhang, L., & Keshavarzian, A. (2003) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.047415 · Cited by 34
Banan, A., Zhang, L.-J., Farhadi, A., Fields, J., Shaikh, M., & Keshavarzian, A. (2004) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00329.2003 · Cited by 31
Quantitative Histomorphometric Study of the Jejunal Mucosa in Chronic Alcoholics
Bode, J. C., Knüppel, H., Schwerk, W. B., Lorenz‐Meyer, H., & Dürr, H. K. (2009) · Digestion · doi:10.1159/000198760 · Cited by 27
Zinc Supplementation in Oral Rehydration Solutions: Experimental Assessment and Mechanisms of Action
Altaf, W., Perveen, S., Rehman, K. U., Teichberg, S., Vancurova, I., Harper, R. G., & Wapnir, R. A. (2002) · Journal of the American College of Nutrition · doi:10.1080/07315724.2002.10719190 · Cited by 22
Kaur, M., Kaur, J., Ojha, S. K., & Mahmood, A. (1998) · Alcohol · doi:10.1016/s0741-8329(97)00099-2 · Cited by 18
Banan, A., Zhang, L. J., Shaikh, M. W., Fields, J. Z., Farhadi, A., & Keshavarzian, A. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.062232 · Cited by 13
Role of Zinc on Lipid Peroxidation and Antioxidative Enzymes in Intestines of Ethanol-Fed Rats
Pathak, A., Mahmood, A., Pathak, R., & Dhawan, D. K. (2004) · Biological Trace Element Research · doi:10.1385/bter:100:3:247 · Cited by 7
Research works printed but not linked: 4
- Banan A, 1999, J Pharmacol Exp Ther, 291, 1075
- 10.1124/jpet.102.047415 · DOI
- Keshavarzian A, 1994, Am J Gastroenterol, 89, 2205
- Keshavarzian A, 2001, J Pharmacol Exp Ther, 299, 442
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Read, S. A., Obeid, S., Ahlenstiel, C., & Ahlenstiel, G. (2019) · Advances in Nutrition · doi:10.1093/advances/nmz013 · Cited by 801
Wang, Y., Kirpich, I., Liu, Y., Ma, Z., Barve, S. S., McClain, C. J., & Feng, W. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.08.039 · Cited by 255
Self-citationMohammad, M. K., Zhou, Z., Cave, M. C., Barve, A. J., & McClain, C. J. (2012) · Nutrition in Clinical Practice · doi:10.1177/0884533611433534 · Cited by 248
Self-citationPotential mechanisms for the emerging link between obesity and increased intestinal permeability
Teixeira, T. F. S., Collado, M. C., Ferreira, C. L. D. L. F., Bressan, J., & Pelúzio, M. D. C. G. (2012) · Nutrition Research · doi:10.1016/j.nutres.2012.07.003 · Cited by 255
Metadata
- 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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