Skip to main content

Advertisement

SpringerLink
Log in

Zinc deficiency as a mediator of toxic effects of alcohol abuse

  • Review
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Grant BF, Goldstein RB, Saha TD, Chou SP, Jung J, Zhang H, Pickering RP, Ruan WJ, Smith SM, Huang B (2015) Epidemiology of DSM-5 alcohol use disorder: results from the national epidemiologic survey on alcohol and related conditions III. JAMA Psychiatry 72:757–766

    PubMed  PubMed Central  Google Scholar 

  2. Organization WH (2011) Global status report on alcohol and health. World Health Organization, Geneva

  3. Shield KD, Parry C, Rehm J (2014) Chronic diseases and conditions related to alcohol use. Alcohol Res 35:155

    PubMed Central  Google Scholar 

  4. Parry CD, Patra J, Rehm J (2011) Alcohol consumption and non-communicable diseases: epidemiology and policy implications. Addiction 106:1718–1724

    PubMed  PubMed Central  Google Scholar 

  5. Mukherjee S (2013) Alcoholism and its effects on the central nervous system. Curr Neurovasc Res 10:256–262

    CAS  PubMed  Google Scholar 

  6. Zahr NM, Pfefferbaum A (2017) Alcohol’s effects on the brain: neuroimaging results in humans and animal models. Alcohol Res Curr Rev 38:183–206

    Google Scholar 

  7. Greenfield SF, Back SE, Lawson K, Brady KT (2010) Substance abuse in women. Psychiatr Clin North Am 33:339–355

    PubMed  PubMed Central  Google Scholar 

  8. Roozen S, Peters GJY, Kok G, Townend D, Nijhuis J, Curfs L (2016) Worldwide prevalence of fetal alcohol spectrum disorders: a systematic literature review including meta-analysis. Alcohol Clin Exp Res 40:18–32

    PubMed  Google Scholar 

  9. Bouchery EE, Harwood HJ, Sacks JJ, Simon CJ, Brewer RD (2011) Economic costs of excessive alcohol consumption in the US, 2006. Am J Prev Med 41:516–524

    PubMed  Google Scholar 

  10. Sacks JJ, Gonzales KR, Bouchery EE, Tomedi LE, Brewer RD (2015) 2010 national and state costs of excessive alcohol consumption. Am J Prev Med 49:e73–e79

    PubMed  Google Scholar 

  11. Badger TM, Ronis MJ, Seitz HK, Albano E, Ingelman-Sundberg M, Lieber CS (2003) Alcohol metabolism: role in toxicity and carcinogenesis. Alcohol Clin Exp Res 27:336–347

    PubMed  Google Scholar 

  12. Cederbaum AI (2012) Alcohol metabolism. Clin Liver Dis 16:667–685

    PubMed  PubMed Central  Google Scholar 

  13. Wu D, Cederbaum AI (2003) Alcohol, oxidative stress, and free radical damage. Alcohol Res Health 27:277–284

    PubMed  Google Scholar 

  14. Mandrekar P, Szabo G (2009) Signalling pathways in alcohol-induced liver inflammation. J Hepatol 50:1258–1266

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Seitz HK, Stickel F (2007) Molecular mechanisms of alcohol-mediated carcinogenesis. Nat Rev Cancer 7:599–612

    CAS  PubMed  Google Scholar 

  16. Seitz H, Suter P (2002) Ethanol toxicity and nutritional status. In: Kotsonis, FN, Mackey, MA (eds) Nutritional toxicology, 2nd edn. Taylor & Francis, New York, pp 122–154

    Google Scholar 

  17. Aaseth J, Ringstad J, Bell H, Thomassen Y (1990) Alcohol, trace elements and liver dysfunction. In: Tomita H (ed) Trace elements in clinical medicine, pp 79–84

    Google Scholar 

  18. Keen CL, Uriu-Adams JY, Skalny A, Grabeklis A, Grabeklis S, Green K, Yevtushok L, Wertelecki WW, Chambers CD (2010) The plausibility of maternal nutritional status being a contributing factor to the risk for fetal alcohol spectrum disorders: the potential influence of zinc status as an example. Biofactors 36:125–135

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Haase H, Rink L (2014) Multiple impacts of zinc on immune function. Metallomics 6:1175–1180

    CAS  PubMed  Google Scholar 

  20. Li YV (2014) Zinc and insulin in pancreatic beta-cells. Endocrine 45:178–189

    CAS  PubMed  Google Scholar 

  21. Foster M, Samman S (2010) Zinc and redox signaling: perturbations associated with cardiovascular disease and diabetes mellitus. Antioxid Redox Signal 13:1549–1573

    CAS  PubMed  Google Scholar 

  22. Marger L, Schubert C, Bertrand D (2014) Zinc: an underappreciated modulatory factor of brain function. Biochem Pharmacol 91:426–435

    CAS  PubMed  Google Scholar 

  23. Prasad AS (2014) Zinc is an antioxidant and anti-inflammatory agent: its role in human health. Front Nutr 1:14

    PubMed  PubMed Central  Google Scholar 

  24. Prasad AS, Halsted JA, Nadimi M (1961) Syndrome of iron deficiency anemia, hepatosplenomegaly, hypogonadism, dwarfism and geophagia. Am J Med 31:532–546

    CAS  PubMed  Google Scholar 

  25. Chasapis CT, Loutsidou AC, Spiliopoulou CA, Stefanidou ME (2012) Zinc and human health: an update. Arch Toxicol 86:521–534

    CAS  PubMed  Google Scholar 

  26. Lieber CS (2000) Alcohol: its metabolism and interaction with nutrients. Annu Rev Nutr 20:395–430

    CAS  PubMed  Google Scholar 

  27. Skalny AV, Kampov-Polevoy AB, Voronin AE (2001) Influence of zinc on ethanol metabolizing enzymes activity in the offspring of rats submitted to the alcohol intoxication. Trace Elem Med (Moscow) 2:21–23

    Google Scholar 

  28. Deshpande JD, Joshi MM, Giri PA (2013) Zinc: the trace element of major importance in human nutrition and health. Int J Med Sci Public Health 2:1–6

    Google Scholar 

  29. Atukorala T, Herath C, Ramachandran S (1986) Zinc and vitamin A status of alcoholics in a medical unit in Sri Lanka. Alcohol Alcohol Suppl 21:269–275

    CAS  Google Scholar 

  30. Avaroglu D, Inal TC, Demir M, Attila G, Acartürk E, Evlice YE, Kayrin L (2005) Biochemical indicators and cardiac function tests in chronic alcohol abusers. Croat Med J 46:233–237

    Google Scholar 

  31. Kiilerich S, Dietrichson O, Loud F, Naestoft J, Christoffersen P, Juhl E, Kjems G, Christiansen C (1980) Zinc depletion in alcoholic liver diseases. Scand J Gastroenterol 15:363–367

    CAS  PubMed  Google Scholar 

  32. Bode JC, Hanisch P, Henning H, Koenig W, Richter FW, Bode C (1988) Hepatic zinc content in patients with various stages of alcoholic liver disease and in patients with chronic active and chronic persistent hepatitis. Hepatology 8:1605–1609

    CAS  PubMed  Google Scholar 

  33. Hartoma TR, Sotaniemi E, Pelkonen O, Ahlqvist J (1977) Serum zinc and serum copper and indices of drug metabolism in alcoholics. Eur J Clin Pharmacol 12:147–151

    CAS  PubMed  Google Scholar 

  34. Rodriguez-Moreno F, González-Reimers E, Santolaria-Fernandez F, Galindo-Martin L, Hernandez-Torres O, Batista-Lopez N, Molina-Perez M (1997) Zinc, copper, manganese, and iron in chronic alcoholic liver disease. Alcohol 14:39–44

    CAS  PubMed  Google Scholar 

  35. Bergheim I, Parlesak A, Dierks C, Bode J, Bode C (2003) Nutritional deficiencies in German middle-class male alcohol consumers: relation to dietary intake and severity of liver disease. Eur J Clin Nutr 57:431

    CAS  PubMed  Google Scholar 

  36. Prystupa A, Błażewicz A, Kiciński P, Sak JJ, Niedziałek J, Załuska W (2016) Serum concentrations of selected heavy metals in patients with alcoholic liver cirrhosis from the Lublin region in Eastern Poland. Int J Environ Res Public Health 13:582

    PubMed Central  Google Scholar 

  37. Zarski J, Arnaud J, Labadie H, Beaugrand M, Favier A, Rachail M (1987) Serum and tissue concentrations of zinc after oral supplementation in chronic alcoholics with or without cirrhosis. Gastroenterol Clin Biol 11:856–860

    CAS  PubMed  Google Scholar 

  38. Wu C-T, Lee J-N, Shen WW, Lee S-L (1984) Serum zinc, copper, and ceruloplasmin levels in male alcoholics. Biol Psychiatry 19:1333–1338

    CAS  PubMed  Google Scholar 

  39. Babenko GA, Skalny AV. Spontaneous and induced chemiluminescence of blood serum at chronic alcoholism. Trace Elem Med (Moscow) 2:46–47

  40. Ahmed SB, Russell RM (1982) The effect of ethanol feeding on zinc balance and tissue zinc levels in rats maintained on zinc-deficient diets. J Lab Clin Med 100:211–217

    CAS  PubMed  Google Scholar 

  41. Wang J, Pierson RN (1975) Distribution of zinc in skeletal muscle and liver tissue in normal and dietary controlled alcoholic rats. J Lab Clin Med 85:50–58

    CAS  PubMed  Google Scholar 

  42. Sullivan JF, Lankford HG (1965) Zinc metabolism and chronic alcoholism. Am J Clin Nutr 17:57–63

    CAS  PubMed  Google Scholar 

  43. Mills PR, Fell GS, Bessent RG, Nelson LM, Russell RI (1983) A study of zinc metabolism in alcoholic cirrhosis. Clin Sci (Lond) 64:527–535

    CAS  Google Scholar 

  44. Manari A, Preedy V, Peters T (2003) Nutritional intake of hazardous drinkers and dependent alcoholics in the UK. Addict Biol 8:201–210

    PubMed  Google Scholar 

  45. Breslow RA, Guenther PM, Juan W, Graubard BI (2010) Alcoholic beverage consumption, nutrient intakes, and diet quality in the US adult population, 1999–2006. J Am Diet Assoc 110:551–562

    PubMed  PubMed Central  Google Scholar 

  46. Dinsmore W, Callender ME, McMaster D, Todd J, Love AH (1985) Zinc absorption in alcoholics using zinc-65. Digestion 32:238–242

    CAS  PubMed  Google Scholar 

  47. Valberg L, Flanagan P, Ghent C, Chamberlain M (1985) Zinc absorption and leukocyte zinc in alcoholic and nonalcoholic cirrhosis. Dig Dis Sci 30:329–333

    CAS  PubMed  Google Scholar 

  48. Skalny A, Berezkina E, Grabeklis A, Kiyaeva E, Tinkov A (2016) Hair trace elements in women with alcohol abuse and their offspring. Trace Elem Electrolytes 33:144

    CAS  Google Scholar 

  49. Skalny AV, Berezkina ES, Kiyaeva EV, Alidzhanova IE, Grabeklis AR, Tinkov AA (2016) The effect of alcohol consumption on maternal and cord blood electrolyte and trace element levels. Acta Sci Pol Technol Aliment 15:439–445

    CAS  PubMed  Google Scholar 

  50. Mancinelli R, Barlocci E, Ciprotti M, Senofonte O, Fidente RM, Draisci R, Attilia ML, Vitali M, Fiore M, Ceccanti M (2013) Blood thiamine, zinc, selenium, lead and oxidative stress in a population of male and female alcoholics: clinical evidence and gender differences. Ann Ist Super Sanita 49:65–72

    CAS  PubMed  Google Scholar 

  51. Gonzalez-Reimers E, Aleman-Valls M, Barroso-Guerrero F, Santolaria-Fernandez F, Lopez-Lirola A, Campelo EG-V, Jarque-Lopez A, Rodriguez-Gaspar M (2002) Hair zinc and copper in chronic alcoholics. Biol Trace Elem Res 85:269

    CAS  PubMed  Google Scholar 

  52. Joshi PC, Guidot DM (2007) The alcoholic lung: epidemiology, pathophysiology, and potential therapies. Am J Physiol Lung Cell Mol Physiol 292:L813–L823

    CAS  PubMed  Google Scholar 

  53. Zalewski PD (2006) Zinc metabolism in the airway: basic mechanisms and drug targets. Curr Opin Pharmacol 6(3):237–243

    CAS  PubMed  Google Scholar 

  54. Zalewski PD, Truong-Tran AQ, Grosser D, Jayaram L, Murgia C, Ruffin RE (2005) Zinc metabolism in airway epithelium and airway inflammation: basic mechanisms and clinical targets. A review. Pharmacol Ther 105(2):127–149

    CAS  PubMed  Google Scholar 

  55. Janssen WJ (2013) Alveolar macrophage dysfunction and chronic alcohol use. Time to think about zinc. Am J Respir Crit Care Med 188:716–723

    Google Scholar 

  56. Curry-McCoy TV, Guidot DM, Joshi PC (2013) Chronic alcohol ingestion in rats decreases Krüppel-like factor 4 expression and intracellular zinc in the lung. Alcohol Clin Exp Res 37:361–371

    CAS  PubMed  Google Scholar 

  57. Joshi PC, Guidot DM (2008) Zinc deficiency suppresses alveolar macrophage function in in vivo models of both chronic alcohol ingestion and HIV-1 transgenic expression. FASEB J 22:856.823

    Google Scholar 

  58. Joshi PC, Mehta A, Jabber WS, Fan X, Guidot DM (2009) Zinc deficiency mediates alcohol-induced alveolar epithelial and macrophage dysfunction in rats. Am J Respir Cell Mol Biol 41:207–216

    CAS  PubMed  Google Scholar 

  59. Mehta AJ, Yeligar SM, Brown LA, Guidot DM (2012) Zinc supplementation in vitro improves immune function and restores intracellular zinc levels in alveolar macrophages isolated from human alcoholics. Recent advances in phagocyte biology. Am Thoracic Soc:A1369–A1369

  60. Mehta AJ, Yeligar SM, Elon L, Brown LA, Guidot DM (2013) Alcoholism causes alveolar macrophage zinc deficiency and immune dysfunction. Am J Respir Crit Care Med 188:716–723

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Vignesh KS, Figueroa JAL, Porollo A, Caruso JA, Deepe GS (2013) Granulocyte macrophage-colony stimulating factor induced Zn sequestration enhances macrophage superoxide and limits intracellular pathogen survival. Immunity 39(4):697–710

    Google Scholar 

  62. Maywald M, Wessels I, Rink L (2017) Zinc signals and immunity. Int J Mol Sci 18(10):2222

    PubMed Central  Google Scholar 

  63. Mehta AJ, Guidot DM (2014) Alcohol-mediated zinc deficiency within the alveolar space: a potential fundamental mechanism underlying oxidative stress and cellular dysfunction in the alcoholic lung.Alcohol use disorders and the lung. Springer, Berlin, pp 173–184

    Google Scholar 

  64. Kloubert V, Rink L (2015) Zinc as a micronutrient and its preventive role of oxidative damage in cells. Food Funct 6(10):3195–3204

    CAS  PubMed  Google Scholar 

  65. Bode C, Bode JC (2003) Effect of alcohol consumption on the gut. Best Pract Res Clin Gastroenterol 17:575–592

    CAS  PubMed  Google Scholar 

  66. Szabo G (2015) Gut–liver axis in alcoholic liver disease. Gastroenterology 148:30–36

    CAS  PubMed  Google Scholar 

  67. Chen P, Schnabl B (2014) Host–microbiome interactions in alcoholic liver disease. Gut liver 8:237

    CAS  PubMed  PubMed Central  Google Scholar 

  68. McClain CJ, Hill DB, Song Z, Deaciuc I, Barve S (2002) Monocyte activation in alcoholic liver disease. Alcohol 27:53–61

    CAS  PubMed  Google Scholar 

  69. Lambert JC, Zhou Z, Wang L, Song Z, McClain CJ, Kang YJ (2003) Prevention of alterations in intestinal permeability is involved in zinc inhibition of acute ethanol-induced liver damage in mice. J Pharmacol Exp Ther 305:880–886

    CAS  PubMed  Google Scholar 

  70. Lambert JC, Zhou Z, Wang L, Song Z, McClain CJ, Kang YJ (2004) Preservation of intestinal structural integrity by zinc is independent of metallothionein in alcohol-intoxicated mice. Am J Pathol 164:1959–1966

    CAS  PubMed  PubMed Central  Google Scholar 

  71. Zhong W, McClain CJ, Cave M, Kang YJ, Zhou Z (2010) The role of zinc deficiency in alcohol-induced intestinal barrier dysfunction. Am J Physiol Gastrointest Liver Physiol 298:G625-G633

    PubMed Central  Google Scholar 

  72. Zhou Z, Zhong W (2012) Zinc and hepatocyte nuclear factor-4α in alcohol-induced intestinal barrier dysfunction. J Epithel Biol Pharmacol 5

    Google Scholar 

  73. Zhong W, Li Q, Sun Q, Zhang W, Zhang J, Sun X, Yin X, Zhang X, Zhou Z (2015) Preventing gut leakiness and endotoxemia contributes to the protective effect of zinc on alcohol-induced steatohepatitis in rats. J Nutr 145:2690–2698

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Singal AK, Kamath PS, Gores GJ, Shah VH (2014) Alcoholic hepatitis: current challenges and future directions. Clin Gastroenterol Hepatol 12:555–564

    PubMed  Google Scholar 

  75. Beier JI, Arteel GE, McClain CJ (2011) Advances in alcoholic liver disease. Curr Gastroenterol Rep 13:56–64

    PubMed  PubMed Central  Google Scholar 

  76. McCullough AJ, O’Shea RS, Dasarathy S (2011) Diagnosis and management of alcoholic liver disease. J Dig Dis 12:257–262

    PubMed  Google Scholar 

  77. Sun Q, Li Q, Zhong W, Zhang J, Sun X, Tan X, Yin X, Sun X, Zhang X, Zhou Z (2014) Dysregulation of hepatic zinc transporters in a mouse model of alcoholic liver disease. Am J Physiol Gastrointest Liver Physiol 307:G313-G322

    PubMed Central  Google Scholar 

  78. Sun Q, Zhong W, Zhang W, Li Q, Sun X, Tan X, Sun X, Dong D, Zhou Z (2015) Zinc deficiency mediates alcohol-induced apoptotic cell death in the liver of rats through activating ER and mitochondrial cell death pathways. Am J Physiol Gastrointest Liver Physiol 308:G757-G766

    PubMed Central  Google Scholar 

  79. Liuzzi J, Yoo C (2013) Role of zinc in the regulation of autophagy during ethanol exposure in human hepatoma cells. Biol Trace Elem Res 156:350–356

    CAS  PubMed  Google Scholar 

  80. Sun Q, Zhong W, Zhang W, Zhou Z (2016) Defect of mitochondrial respiratory chain is a mechanism of ROS overproduction in a rat model of alcoholic liver disease: role of zinc deficiency. Am J Physiol Gastrointest Liver Physiol 310:G205–G214

    Google Scholar 

  81. Kang X, Song Z, McClain CJ, Kang YJ, Zhou Z (2008) Zinc supplementation enhances hepatic regeneration by preserving hepatocyte nuclear factor-4α in mice subjected to long-term ethanol administration. Am J Pathol 172:916–925

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Zhong W, Zhao Y, Sun X, Song Z, McClain CJ, Zhou Z (2013) Dietary zinc deficiency exaggerates ethanol-induced liver injury in mice: involvement of intrahepatic and extrahepatic factors. PloS One 8:e76522

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Zhao Y, Zhong W, Sun X, Song Z, Clemens DL, Kang YJ, McClain CJ, Zhou Z (2011) Zinc deprivation mediates alcohol-induced hepatocyte IL-8 analog expression in rodents via an epigenetic mechanism. Am J Pathol 179:693–702

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Moghe A, Joshi-Barve S, Ghare S, Gobejishvili L, Kirpich I, McClain CJ, Barve S (2011) Histone modifications and alcohol-induced liver disease: are altered nutrients the missing link? World J Gastroenterol 17:2465

    PubMed  PubMed Central  Google Scholar 

  85. Kotegov VP, Skalny AV, Brudastov JA, Suldin AV, Malkova JG (2012) Research of action of zinc sulphate on glucose tolerance, hypoglycemic effect of insulin and ethanol toxicity. Prob Biol Med Pharm Chem 6:63–67

    Google Scholar 

  86. Xiao M, Liu C, Sun W, Dong M, Hu G, Li J (2012) Zinc supplementation effects on alcoholic liver disease and the molecular mechanism. Zhongguo Ying Yong Sheng Li Xue Za Zhi 28:84–88

    CAS  PubMed  Google Scholar 

  87. Szuster-Ciesielska A, Plewka K, Daniluk J, Kandefer-Szerszeń M (2009) Zinc supplementation attenuates ethanol-and acetaldehyde-induced liver stellate cell activation by inhibiting reactive oxygen species (ROS) production and by influencing intracellular signaling. Biochem Pharmacol 78:301–314

    CAS  PubMed  Google Scholar 

  88. Kang X, Zhong W, Liu J, Song Z, McClain CJ, Kang YJ, Zhou Z (2009) Zinc supplementation reverses alcohol-induced steatosis in mice through reactivating hepatocyte nuclear factor-4α and peroxisome proliferator-activated receptor-α. Hepatology 50:1241–1250

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Zhou Z, Liu J, Song Z, McClain CJ, Kang YJ (2008) Zinc supplementation inhibits hepatic apoptosis in mice subjected to a long-term ethanol exposure. Exp Biol Med (Maywood) 233:540–548

    CAS  Google Scholar 

  90. Zhou Z, Sun X, Lambert JC, Saari JT, Kang YJ (2002) Metallothionein-independent zinc protection from alcoholic liver injury. Am J Pathol 160:2267–2274

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Zhou Z, Wang L, Song Z, Saari JT, McClain CJ, Kang YJ (2005) Zinc supplementation prevents alcoholic liver injury in mice through attenuation of oxidative stress. Am J Pathol 166:1681–1690

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Mohammad MK, Falkner KC, Song M, McClain CJ, Cave MC (2015) Low dose zinc sulfate (220 mg) supplementation for three months normalizes zinc levels, endotoxeima, pro-inflammatory/fibrotic biomarkers & improves clinical parameters in alcoholic cirrhosis-a double-blind placebo controlled-(ZAC) clinical trial. Hepatology 62:851A–852A

    Google Scholar 

  93. Weismann K, Christensen E, Dreyer V (1979) Zinc supplementation in alcoholic cirrhosis. J Intern Med 205:361–366

    CAS  Google Scholar 

  94. Liu J, Lewohl JM, Harris RA, Dodd PR, Mayfield RD (2007) Altered gene expression profiles in the frontal cortex of cirrhotic alcoholics. Alcohol Clin Exp Res 31:1460–1466

    CAS  PubMed  Google Scholar 

  95. Gonzalez-Reimers E, Durán-Castellón M, Martín-Olivera R, López-Lirola A, Santolaria-Fernández F, De la Vega-Prieto M, Pérez-Ramírez A, Campelo EG-V (2005) Effect of zinc supplementation on ethanol-mediated bone alterations. Food Chem Toxicol 43:1497–1505

    CAS  PubMed  Google Scholar 

  96. González-Reimers E, Santolaria-Fernández F (2011) Brain atrophy in alcoholics. Handbook of behavior, food and nutrition. Springer, Berlin, pp 2993–3010

    Google Scholar 

  97. Skal’nyi A, Kukhtina E, Ol’khovskaya I, Glushchenko N (1992) Reduction of voluntary ethanol consumption by a long-acting zinc preparation. Bull Exp Biol Med 113:506–509

    Google Scholar 

  98. Morud J, Adermark L, Ericson M, Söderpalm B (2015) Alterations in ethanol-induced accumbal transmission after acute and long-term zinc depletion. Addict Biol 20:170–181

    CAS  PubMed  Google Scholar 

  99. McCracken LM, Trudell JR, Goldstein BE, Harris RA, Mihic SJ (2010) Zinc enhances ethanol modulation of the α1 glycine receptor. Neuropharmacology 58:676–681

    CAS  PubMed  Google Scholar 

  100. McCracken LM, Blednov YA, Trudell JR, Benavidez JM, Betz H, Harris RA (2013) Mutation of a zinc-binding residue in the glycine receptor α1 subunit changes ethanol sensitivity in vitro and alcohol consumption in vivo. J Pharmacol Exp Ther 344:489–500

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Skalny A, Kampov-Polevoy A (1988) Zinc sulfate in the prevention of alcohol motivation in rats. Biull Eksp Biol Med 105

  102. Vyatchanina ES, Skalny AV (2007) Protectant action of zinc sulfate at intrauterine alcohol influence. Vestnik Orenburg State Univ 12:113–116

    Google Scholar 

  103. Vyatchanina ES (2011) Preconceptional alcoholic intoxication alters the distribution of metals in matured rat brain of offspring. J Trace Elem Med Biol 25:S59–S62

    CAS  PubMed  Google Scholar 

  104. Maksymovych I, Kharchenko O, Chaika V, Gadilia O, Ostapchenko L (2010) Nitric oxide synthase activity in liver and brain cells under development of chronic alcoholic intoxication and zinc acetate treatment. Alcohol Clin Exp Res 34:168A

    Google Scholar 

  105. Sensi SL, Paoletti P, Koh J-Y, Aizenman E, Bush AI, Hershfinkel M (2011) The neurophysiology and pathology of brain zinc. J Neurosci 31:16076–16085

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Takuma Y, Nouso K, Makino Y, Hayashi M, Takahashi H (2010) Clinical trial: oral zinc in hepatic encephalopathy. Aliment Pharmacol Ther 32:1080–1090

    CAS  PubMed  Google Scholar 

  107. Uriu-Adams JY, Keen CL (2010) Zinc and reproduction: effects of zinc deficiency on prenatal and early postnatal development. Birth Defects Res B Dev Reprod Toxicol 89:313–325

    CAS  PubMed  Google Scholar 

  108. May PA, Gossage JP (2011) Maternal risk factors for fetal alcohol spectrum disorders: not as simple as it might seem. Alcohol Res Health 34:15

    PubMed  PubMed Central  Google Scholar 

  109. Miller SI, Del Villano BC, Flynn A, Krumhansl M (1983) Interaction of alcohol and zinc in fetal dysmorphogenesis. Pharmacol Biochem Behav 18:311–315

    CAS  PubMed  Google Scholar 

  110. Carey LC, Coyle P, Philcox JC, Rofe AM (2003) Zinc supplementation at the time of ethanol exposure ameliorates teratogenicity in mice. Alcohol Clin Exp Res 27:107–110

    CAS  PubMed  Google Scholar 

  111. Flynn A, Martier S, Sokol R, Miller S, Golden N, Del Villano B (1981) Zinc status of pregnant alcoholic women: a determinant of fetal outcome. Lancet 317:572–575

    Google Scholar 

  112. Ghishan FK, Patwardhan R, Greene HL (1982) Fetal alcohol syndrome: inhibition of placental zinc transport as a potential mechanism for fetal growth retardation in the rat. J Lab Clin Med 100:45–52

    CAS  PubMed  Google Scholar 

  113. Ghishan FK, Greene HL (1983) Fetal alcohol syndrome: failure of zinc supplementation to reverse the effect of ethanol on placental transport of zinc. Pediatr Res 17:529–531

    CAS  PubMed  Google Scholar 

  114. Skalny AV (1987) Zinc deficiency in mothers and their offspring in alcohol abuse. Akush Gynecol 4:6–8

    Google Scholar 

  115. Murillo-Fuentes M, Reyes A, MaLuisa O, Murillo M, Carreras O (2010) Different effects on zinc redistribution if ethanol is consumed before or immediately after birth. J Trace Elem Med Biol 24:200–206

    CAS  PubMed  Google Scholar 

  116. Skalny AV, Slavin FI (1988) Mineral exchange and tissue-specific cytotoxic activity of blood serum in offspring at chronic alcohol intoxication in parents. S. S. Korsakov J Neurol Psychiatry 88:107–109

    Google Scholar 

  117. Carey LC, Coyle P, Philcox JC, Rofe AM (2000) Ethanol decreases zinc transfer to the fetus in normal but not metallothionein-null mice. Alcohol Clin Exp Res 24:1236–1240

    CAS  PubMed  Google Scholar 

  118. Coyle P, Martin SA, Carey LC, Summers BL, Rofe AM (2009) Ethanol-mediated fetal dysmorphology and its relationship to the ontogeny of maternal liver metallothionein. Alcohol Clin Exp Res 33:1051–1058

    CAS  PubMed  Google Scholar 

  119. Samson HH, Diaz J (1981) Altered development of brain by neonatal ethanol exposure: zinc levels during and after exposure. Alcohol Clin Exp Res 5:563–569

    CAS  PubMed  Google Scholar 

  120. Chen WJA, Berryhill EC, West JR (2001) Zinc supplementation does not attenuate alcohol-induced cerebellar Purkinje cell loss during the brain growth spurt period. Alcohol Clin Exp Res 25:600–605

    CAS  PubMed  Google Scholar 

  121. González-Reimers E, Santolaria-Fernández F, Alvisa-Negrín J (2013) Bone changes in alcoholics: a review. Alcohol 1:16

    Google Scholar 

  122. Ineu RP, Oliveira CS, Oliveira VA, Moraes-Silva L, da Luz SCA, Pereira ME (2013) Antioxidant effect of zinc chloride against ethanol-induced gastrointestinal lesions in rats. Food Chem Toxicol 58:522–529

    CAS  PubMed  Google Scholar 

  123. Awtry EH, Philippides GJ (2010) Alcoholic and cocaine-associated cardiomyopathies. Prog Cardiovasc Dis 52:289–299

    PubMed  Google Scholar 

  124. Wang L, Zhou Z, Saari JT, Kang YJ (2005) Alcohol-induced myocardial fibrosis in metallothionein-null mice: prevention by zinc supplementation. Am J Pathol 167:337–344

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Pathak R, Dhawan D, Pathak A (2011) Effect of zinc supplementation on the status of thyroid hormones and Na, K, and Ca levels in blood following ethanol feeding. Biol Trace Elem Res 140:208–214

    CAS  PubMed  Google Scholar 

  126. Castellón MD, González-Reimers E, López-Lirola A, Olivera RM, Santolaria-Fernández F, Galindo-Martín L, Abreu-González P, González-Hernández T (2005) Alcoholic myopathy: lack of effect of zinc supplementation. Food Chem Toxicol 43:1333–1343

    Google Scholar 

  127. Jung MK, Callaci JJ, Lauing KL, Otis JS, Radek KA, Jones MK, Kovacs EJ (2011) Alcohol exposure and mechanisms of tissue injury and repair. Alcohol Clin Exp Res 35:392–399

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The current investigation is supported by the Russian Foundation for Basic Research within Project No. 15-04-08621.

Author information

Authors and Affiliations

  1. Yaroslavl State University, Sovetskaya St., 14, Yaroslavl, 150000, Russia

    Anatoly V. Skalny, Andrei R. Grabeklis & Alexey A. Tinkov

  2. Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya St., 6, Moscow, 105064, Russian Federation

    Anatoly V. Skalny, Margarita G. Skalnaya, Andrei R. Grabeklis & Alexey A. Tinkov

  3. Orenburg State University, Pobedy Ave., 13, Orenburg, 460352, Russia

    Anatoly V. Skalny

  4. Trace Element Institute for UNESCO, Lyon, France

    Anatoly V. Skalny

  5. Lomonosov Moscow State University, Leninskie Gory, 1, Moscow, 119991, Russia

    Anastasia A. Skalnaya

  6. Institute of Cellular and Intracellular Symbiosis, Russian Academy of Sciences, Pionerskaya St., 11, Orenburg, 460000, Russia

    Alexey A. Tinkov

Authors
  1. Anatoly V. Skalny
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Margarita G. Skalnaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Andrei R. Grabeklis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anastasia A. Skalnaya
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Alexey A. Tinkov
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexey A. Tinkov.

Ethics declarations

Conflict of interest

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Skalny, A.V., Skalnaya, M.G., Grabeklis, A.R. et al. Zinc deficiency as a mediator of toxic effects of alcohol abuse. Eur J Nutr 57, 2313–2322 (2018). https://doi.org/10.1007/s00394-017-1584-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-017-1584-y

Keywords

Search

Navigation