Zinc deficiency as a mediator of toxic effects of alcohol abuse

Objective: To review data on the role of ethanol-induced alteration of Zn homeostasis in mediation of adverse effects of alcohol abuse. Methods: The scholarly published articles on the association between Zn metabolism and alcohol-associated disorders (liver, brain, lung, gut dysfunction, and fetal alcohol syndrome) have been reviewed. Results: It is demonstrated that alcohol-induced modulation of zinc transporters results in decreased Zn levels in lungs, liver, gut, and brain. Zn deficiency in the gut results in increased gut permeability, ultimately leading to endotoxemia and systemic inflammation. Similarly, Zn deficiency in lung epithelia and alveolar macrophages decreases lung barrier function resulting in respiratory distress syndrome. In turn, increased endotoxemia significantly contributes to proinflammatory state in alcoholic liver disease. Finally, impaired gut and liver functions may play a significant role in alcoholic brain damage, being associated with both increased proinflammatory signaling and accumulation of neurotoxic metabolites. It is also hypothesized that ethanol-induced Zn deficiency may interfere with neurotransmission. Similar changes may take place in the fetus as a result of impaired placental zinc transfer, maternal zinc deficiency, or maternal Zn sequestration, resulting in fetal alcoholic syndrome. Therefore, alcoholic Zn deficiency not only mediates the adverse effects of ethanol exposure, but also provides an additional link between different alcohol-induced disorders. Conclusions: Generally, current findings suggest that assessment of Zn status could be used as a diagnostic marker of metabolic disturbances in alcohol abuse, whereas modulation of Zn metabolism may be a potential tool in the treatment of alcohol-associated disorders. © 2017, Springer-Verlag GmbH Germany, part of Springer Nature.

Skalny A.V. 1, 2, 3, 4 , Skalnaya M.G. 2 , Grabeklis A.R. 1, 2 , Skalnaya A.A.5 , Tinkov A.A. 1, 2, 6
Dr. Dietrich Steinkopff Verlag GmbH and Co. KG
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  • 1 Yaroslavl State University, Sovetskaya St., 14, Yaroslavl, 150000, Russian Federation
  • 2 Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya St., 6, Moscow, 105064, Russian Federation
  • 3 Orenburg State University, Pobedy Ave., 13, Orenburg, 460352, Russian Federation
  • 4 Trace Element Institute for UNESCO, Lyon, France
  • 5 Lomonosov Moscow State University, Leninskie Gory, 1, Moscow, 119991, Russian Federation
  • 6 Institute of Cellular and Intracellular Symbiosis, Russian Academy of Sciences, Pionerskaya St., 11, Orenburg, 460000, Russian Federation
Ключевые слова
Endotoxemia; Ethanol; Gut permeability; Inflammation; Zinc
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