Digestive Diseases and Sciences

, Volume 52, Issue 7, pp 1595–1612 | Cite as

Zinc and the Liver: An Active Interaction

  • Ioannis Stamoulis
  • Grigorios Kouraklis
  • Stamatios Theocharis
Review article


Zinc is an essential trace element, exerting important antioxidant, anti-inflammatory, and antiapoptotic effects. It affects growth and development and participates in processes such as aging and cancer induction. The liver is important for the regulation of zinc homeostasis, while zinc is necessary for proper liver function. Decreased zinc levels have been implicated in both acute and chronic liver disease states, and zinc deficiency has been implicated in the pathogenesis of liver diseases. Zinc supplementation offers protection in experimental animal models of acute and chronic liver injury, but these hepatoprotective properties have not been fully elucidated. In the present review, data on zinc homeostasis, its implication in the pathogenesis of liver diseases, and its effect on acute and chronic liver diseases are presented. It is concluded that zinc could protect against liver diseases, although up to now the underlying pathophysiology of zinc and liver interactions have not been defined.


Zinc Liver Injury Acute Chronic Hepatocellular carcinoma 


  1. 1.
    Maret W (2005) Zinc coordination environments in proteins determine zinc functions. J Trace Elem Med Biol 19:7–12PubMedGoogle Scholar
  2. 2.
    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 105:127–149PubMedGoogle Scholar
  3. 3.
    Tudor R, Zalewski PD, Ratnaike RN (2005) Zinc in health and chronic disease. J Nutr Health Aging 9:45–51PubMedGoogle Scholar
  4. 4.
    Mocchegiani E, Bertoni-Freddari C, Marcellini F, Malavolta M (2005) Brain, aging and neurodegeneration: role of zinc ion availability. Prog Neurobiol 75:367–390PubMedGoogle Scholar
  5. 5.
    Hambidge M, Krebs NF (2001) Interrelationships of key variables of human zinc homeostasis: relevance to dietary zinc requirements. Annu Rev Nutr 21:429–452PubMedGoogle Scholar
  6. 6.
    Favier M, Hininger-Favier I (2005) [Zinc and pregnancy]. Gynecol Obstet Fertil 33:253–258PubMedGoogle Scholar
  7. 7.
    MacDonald RS (2000) The role of zinc in growth and cell proliferation. J Nutr 130:1500S–1508SPubMedGoogle Scholar
  8. 8.
    Ganss B, Jheon A (2004) Zinc finger transcription factors in skeletal development. Crit Rev Oral Biol Med 15:282–297PubMedGoogle Scholar
  9. 9.
    Brown KH, Peerson JM, Rivera J, Allen LH (2002) Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta-analysis of randomized controlled trials. Am J Clin Nutr 75:1062–1071PubMedGoogle Scholar
  10. 10.
    Stehbens W (2003) Oxidative stress, toxic hepatitis, and antioxidants with particular emphasis on zinc. Exp Mol Pathol 75:265–276PubMedGoogle Scholar
  11. 11.
    DiSilvestro RA (2000) Zinc in relation to diabetes and oxidative disease. J Nutr 130:1509S–1511SPubMedGoogle Scholar
  12. 12.
    Prasad AS, Bao B, Beck FW, Kucuk O, Sarkar FH (2004) Antioxidant effect of zinc in humans. Free Radic Biol Med 37:1182–1190PubMedGoogle Scholar
  13. 13.
    Powell SR (2000) The antioxidant properties of zinc. J Nutr 130:1447S–1454SPubMedGoogle Scholar
  14. 14.
    Andrews GK (2001) Cellular zinc sensors: MTF-1 regulation of gene expression. Biometals 14:223–237PubMedGoogle Scholar
  15. 15.
    Theocharis SE, Margeli AP, Koutselinis A (2003) Metallothionein: a multifunctional protein from toxicity to cancer. Int J Biol Markers 18:162–169PubMedGoogle Scholar
  16. 16.
    Theocharis SE, Margeli AP, Klijanienko JT, Kouraklis GP (2004) Metallothionein expression in human neoplasia. Histopathology 45:103–118PubMedGoogle Scholar
  17. 17.
    Oteiza PI, Mackenzie GG (2005) Zinc, oxidant-triggered cell signaling, and human health. Mol Aspects Med 26:245–255PubMedGoogle Scholar
  18. 18.
    Parsons SE, DiSilvestro RA (1994) Effects of mild zinc deficiency, plus or minus an acute-phase response, on galactosamine-induced hepatitis in rats. Br J Nutr 72:611–618PubMedGoogle Scholar
  19. 19.
    Thiele DJ (2003) Integrating trace element metabolism from cell to the whole organism. J Nutr 133:1579S–1580SPubMedGoogle Scholar
  20. 20.
    Shim H, Leah Harris Z (2003) Genetic defects in copper metabolism. J Nutr 133:1527S–1531SPubMedGoogle Scholar
  21. 21.
    Barceloux DG (1999) Copper. J Toxicol Clin Toxicol 37:217–230PubMedGoogle Scholar
  22. 22.
    Hatano R, Ebara M, Fukuda H, Yoshikawa M, Sugiura N, Kondo F, Yukawa M, Saisho H (2000) Accumulation of copper in the liver and hepatic injury in chronic hepatitis C. J Gastroenterol Hepatol 15:786–791PubMedGoogle Scholar
  23. 23.
    Bogden JD (2004) Influence of zinc on immunity in the elderly. J Nutr Health Aging 8:48–54PubMedGoogle Scholar
  24. 24.
    Cuevas LE, Koyanagi A (2005) Zinc and infection: a review. Ann Trop Paediatr 25:149–160PubMedGoogle Scholar
  25. 25.
    Fraker PJ, King LE (2004) Reprogramming of the immune system during zinc deficiency. Annu Rev Nutr 24:277–298PubMedGoogle Scholar
  26. 26.
    Prasad AS, Bao B, Beck FW, Sarkar FH (2001) Zinc activates NF-kappaB in HUT-78 cells. J Lab Clin Med 138:250–256PubMedGoogle Scholar
  27. 27.
    Truong-Tran AQ, Carter J, Ruffin RE, Zalewski PD (2001) The role of zinc in caspase activation and apoptotic cell death. Biometals 14:315–330PubMedGoogle Scholar
  28. 28.
    Pal S, He K, Aizenman E (2004) Nitrosative stress and potassium channel-mediated neuronal apoptosis: is zinc the link? Pflugers Arch 448:296–303PubMedGoogle Scholar
  29. 29.
    Fraker PJ (2005) Roles for cell death in zinc deficiency. J Nutr 135:359–362PubMedGoogle Scholar
  30. 30.
    Truong-Tran AQ, Grosser D, Ruffin RE, Murgia C, Zalewski PD (2003) Apoptosis in the normal and inflamed airway epithelium: role of zinc in epithelial protection and procaspase-3 regulation. Biochem Pharmacol 66:1459–1468PubMedGoogle Scholar
  31. 31.
    Chandra RK (2004) Impact of nutritional status and nutrient supplements on immune responses and incidence of infection in older individuals. Ageing Res Rev 3:91–104PubMedGoogle Scholar
  32. 32.
    Ames BN (2004) A role for supplements in optimizing health: the metabolic tune-up. Arch Biochem Biophys 423:227–234PubMedGoogle Scholar
  33. 33.
    Fenech M (2002) Micronutrients and genomic stability: a new paradigm for recommended dietary allowances (RDAs). Food Chem Toxicol 40:1113–1117PubMedGoogle Scholar
  34. 34.
    Ames BN (2004) Delaying the mitochondrial decay of aging. Ann N Y Acad Sci 1019:406–411PubMedGoogle Scholar
  35. 35.
    Atamna H (2004) Heme, iron, and the mitochondrial decay of ageing. Ageing Res Rev 3:303–318PubMedGoogle Scholar
  36. 36.
    Prasad AS, Kucuk O (2002) Zinc in cancer prevention. Cancer Metastasis Rev 21:291–295PubMedGoogle Scholar
  37. 37.
    Philpott M, Ferguson LR (2004) Immunonutrition and cancer. Mutat Res 551:29–42PubMedGoogle Scholar
  38. 38.
    Krebs NE, Hambidge KM (2001) Zinc metabolism and homeostasis: the application of tracer techniques to human zinc physiology. Biometals 14:397–412PubMedGoogle Scholar
  39. 39.
    King JC (2001) Effect of acute zinc depletion on zinc homeostasis and plasma zinc kinetics in men. Am J Clin Nutr 74:116–124PubMedGoogle Scholar
  40. 40.
    King JC, Shames DM, Woodhouse LR (2000) Zinc homeostasis in humans. J Nutr 130:1360S–1366SPubMedGoogle Scholar
  41. 41.
    Maret W (2003) Cellular zinc and redox states converge in the metallothionein/thionein pair. J Nutr 133:1460S–1462SPubMedGoogle Scholar
  42. 42.
    Henkel G, Krebs B (2004) Metallothioneins: zinc, cadmium, mercury, and copper thiolates and selenolates mimicking protein active site features–structural aspects and biological implications. Chem Rev 104:801–824PubMedGoogle Scholar
  43. 43.
    Eide DJ (2003) Multiple regulatory mechanisms maintain zinc homeostasis in Saccharomyces cerevisiae. J Nutr 133:1532S–1535SPubMedGoogle Scholar
  44. 44.
    Grungreiff K (2002) Zinc in liver disease. J Trace Elem Exp Med 15:67–78Google Scholar
  45. 45.
    Xu Z, Squires EJ, Bray TM (1994) Effects of dietary zinc deficiency on the hepatic microsomal cytochrome P450 2B in rats. Can J Physiol Pharmacol 72:211–216PubMedGoogle Scholar
  46. 46.
    Fota-Markowska H, Przybyla A, Borowicz I, Modrzewska R (2002) Serum zinc (Zn) level dynamics in blood serum of patients with acute viral hepatitis B and early recovery period. Ann Univ Mariae Curie Sklodowska [Med] 57:201–209Google Scholar
  47. 47.
    Kalkan A, Bulut V, Avci S, Celik I, Bingol NK (2002) Trace elements in viral hepatitis. J Trace Elem Med Biol 16:227–230PubMedGoogle Scholar
  48. 48.
    Stehbens WE (2004) Oxidative stress in viral hepatitis and AIDS. Exp Mol Pathol 77:121–132PubMedGoogle Scholar
  49. 49.
    Pramoolsinsap C, Promvanit N, Kurathong S (1996) Serum trace metal levels in patients with acute hepatitis B. Southeast Asian J Trop Med Public Health 27:476–480PubMedGoogle Scholar
  50. 50.
    Tellinghuisen TL, Marcotrigiano J, Gorbalenya AE, Rice CM (2004) The NS5A protein of hepatitis C virus is a zinc metalloprotein. J Biol Chem 279:48576–48587PubMedGoogle Scholar
  51. 51.
    De Francesco R, Pessi A, Steinkuhler C (1998) The hepatitis C virus NS3 proteinase: structure and function of a zinc-containing serine proteinase. Antivir Ther 3(Suppl 3):99–109PubMedGoogle Scholar
  52. 52.
    De Francesco R, Pessi A, Steinkuhler C (1999) Mechanisms of hepatitis C virus NS3 proteinase inhibitors. J Viral Hepat 6(Suppl 1):23–30PubMedGoogle Scholar
  53. 53.
    Kiilerich S, Dietrichson O, Loud FB, Naestoft J, Christoffersen P, Juhl E, Kjems G, Christiansen C (1980) Zinc depletion in alcoholic liver diseases. Scand J Gastroenterol 15:363–367PubMedGoogle Scholar
  54. 54.
    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 8:1605–1609PubMedGoogle Scholar
  55. 55.
    Mikhail TH, Nicola WG, Ibrahim KH, Salama SH, Emam M (1996) Abnormal zinc and copper metabolism in hepatic steatosis. Boll Chim Farm 135:591–597PubMedGoogle Scholar
  56. 56.
    Polavarapu R, Spitz DR, Sim JE, Follansbee MH, Oberley LW, Rahemtulla A, Nanji AA (1998) Increased lipid peroxidation and impaired antioxidant enzyme function is associated with pathological liver injury in experimental alcoholic liver disease in rats fed diets high in corn oil and fish oil. Hepatology 27:1317–1323PubMedGoogle Scholar
  57. 57.
    Kang YJ, Zhou Z (2005) Zinc prevention and treatment of alcoholic liver disease. Mol Aspects Med 26:391–404PubMedGoogle Scholar
  58. 58.
    Chetri K, Choudhuri G (2003) Role of trace elements in hepatic encephalopathy: zinc and manganese. Indian J Gastroenterol 22(Suppl 2):S28–S30PubMedGoogle Scholar
  59. 59.
    Loomba V, Pawar G, Dhar KL, Setia MS (1995) Serum zinc levels in hepatic encephalopathy. Indian J Gastroenterol 14:51–53PubMedGoogle Scholar
  60. 60.
    DiSilvestro RA, Carlson GP (1994) Effects of mild zinc deficiency, plus or minus acute phase response, on CCl4 hepatotoxicity. Free Radic Biol Med 16:57–61PubMedGoogle Scholar
  61. 61.
    Cagen SZ, Klaassen CD (1979) Protection of carbon tetrachloride-induced hepatotoxicity by zinc: role of metallothionein. Toxicol Appl Pharmacol 51:107–116PubMedGoogle Scholar
  62. 62.
    Itoh N, Kimura T, Nakanishi H, Muto N, Kobayashi M, Kitagawa I, Tanaka K (1997) Metallothionein-independent hepatoprotection by zinc and sakuraso-saponin. Toxicol Lett 93:135–140PubMedGoogle Scholar
  63. 63.
    Zhou Z, Sun X, Lambert JC, Saari JT, Kang YJ (2002) Metallothionein-independent zinc protection from alcoholic liver injury. Am J Pathol 160:2267–2274PubMedGoogle Scholar
  64. 64.
    Ademuyiwa O, Onitilo O, Dosumu O, Ayannuga O, Bakare A, Akinlatun W, Ogunyemi EO (2002) Zinc in CCl4 toxicity. Biomed Environ Sci 15:187–195PubMedGoogle Scholar
  65. 65.
    Cagen SZ, Klaasen CD (1980) Carbon tetrachloride-induced hepatotoxicity: studies in developing rats and protection by zinc. Fed Proc 39:3124–3128PubMedGoogle Scholar
  66. 66.
    Cabre M, Ferre N, Folch J, Paternain JL, Hernandez M, del Castillo D, Joven J, Camps J (1999) Inhibition of hepatic cell nuclear DNA fragmentation by zinc in carbon tetrachloride-treated rats. J Hepatol 31:228–234PubMedGoogle Scholar
  67. 67.
    Medici V, Sturniolo GC, Santon A, D’Inca R, Bortolami M, Cardin R, Basso D, Albergoni V, Irato P (2005) Efficacy of zinc supplementation in preventing acute hepatitis in Long-Evans Cinnamon rats. Liver Int 25:888–895PubMedGoogle Scholar
  68. 68.
    Theocharis SE, Margeli AP, Skaltsas SD, Spiliopoulou CA, Koutselinis AS (2001) Induction of metallothionein in the liver of carbon tetrachloride intoxicated rats: an immunohistochemical study. Toxicology 161:129–138PubMedGoogle Scholar
  69. 69.
    Theocharis SE, Kanelli H, Margeli AP, Spiliopoulou CA, Koutselinis AS (2000) Metallothionein and heat shock protein expression during acute liver injury and regeneration in rats. Clin Chem Lab Med 38:1137–1140PubMedGoogle Scholar
  70. 70.
    Davis SR, Samuelson DA, Cousins RJ (2001) Metallothionein expression protects against carbon tetrachloride-induced hepatotoxicity, but overexpression and dietary zinc supplementation provide no further protection in metallothionein transgenic and knockout mice. J Nutr 131:215–222PubMedGoogle Scholar
  71. 71.
    Jiang Y, Kang YJ (2004) Metallothionein gene therapy for chemical-induced liver fibrosis in mice. Mol Ther 10:1130–1139PubMedGoogle Scholar
  72. 72.
    Srinivasan S, Balwani JH (1969) Effect of zinc sulphate on carbon tetrachloride hepatotoxicity. Acta Pharmacol Toxicol (Copenh) 27:424–428Google Scholar
  73. 73.
    Khoo C, Hallquist NA, Samuelson DA, Cousins RJ (1996) Differential expression of cysteine-rich intestinal protein in liver and intestine in CCl4-induced inflammation. Am J Physiol 270:G613–G618PubMedGoogle Scholar
  74. 74.
    Pinzani M, Rombouts K (2004) Liver fibrosis: from the bench to clinical targets. Dig Liver Dis 36:231–242PubMedGoogle Scholar
  75. 75.
    Capocaccia L, Merli M, Piat C, Servi R, Zullo A, Riggio O (1991) Zinc and other trace elements in liver cirrhosis. Ital J Gastroenterol 23:386–391PubMedGoogle Scholar
  76. 76.
    Leveille CR, Arias IM (1993) Pathophysiology and pharmacologic modulation of hepatic fibrosis. J Vet Intern Med 7:73–84PubMedGoogle Scholar
  77. 77.
    Blei AT, Cordoba J (2001) Hepatic encephalopathy. Am J Gastroenterol 96:1968–1976PubMedGoogle Scholar
  78. 78.
    Rocchi E, Borella P, Borghi A, Paolillo F, Pradelli M, Farina F, Casalgrandi G (1994) Zinc and magnesium in liver cirrhosis. Eur J Clin Invest 24:149–155PubMedGoogle Scholar
  79. 79.
    Poo JL, Rosas-Romero R, Rodriguez F, Silencio JL, Munoz R, Bourges H, Uribe M (1995) Serum zinc concentrations in two cohorts of 153 healthy subjects and 100 cirrhotic patients from Mexico City. Dig Dis 13:136–142PubMedGoogle Scholar
  80. 80.
    Barry M, Keeling PW, Feely J (1990) Tissue zinc status and drug elimination in patients with chronic liver disease. Clin Sci (Lond) 78:547–549Google Scholar
  81. 81.
    Goode HF, Kelleher J, Walker BE (1990) Relation between zinc status and hepatic functional reserve in patients with liver disease. Gut 31:694–697PubMedGoogle Scholar
  82. 82.
    Pramoolsinsap C, Promvanit N, Komindr S, Lerdverasirikul P, Srianujata S (1994) Serum trace metals in chronic viral hepatitis and hepatocellular carcinoma in Thailand. J Gastroenterol 29:610–615PubMedGoogle Scholar
  83. 83.
    Gil Extremera B, Maldonado Martin A, Ruiz Martinez M, Cantero Hinojosa J, Diez Ruiz A, Rodrigo Moreno MD (1990) Zinc and liver cirrhosis. Acta Gastroenterol Belg 53:292–298PubMedGoogle Scholar
  84. 84.
    Scholmerich J, Becher MS, Kottgen E, Rauch N, Haussinger D, Lohle E, Vuilleumier JP, Gerok W (1983) The influence of portosystemic shunting on zinc and vitamin A metabolism in liver cirrhosis. Hepatogastroenterology 30:143–147PubMedGoogle Scholar
  85. 85.
    Keeling PW, Jones RB, Hilton PJ, Thompson RP (1980) Reduced leucocyte zinc in liver disease. Gut 21:561–564PubMedGoogle Scholar
  86. 86.
    Gur G, Bayraktar Y, Ozer D, Ozdogan M, Kayhan B (1998) Determination of hepatic zinc content in chronic liver disease due to hepatitis B virus. Hepatogastroenterology 45:472–476PubMedGoogle Scholar
  87. 87.
    Ozbal E, Helvaci M, Kasirga E, Akdenizoglu F, Kizilgunesler A (2002) Serum zinc as a factor predicting response to interferon-alpha2b therapy in children with chronic hepatitis B. Biol Trace Elem Res 90:31–38PubMedGoogle Scholar
  88. 88.
    Sriramachari S, Tandon BN, Acharya SK (1996) Excess zinc and progressive cholestasis: a new disease? Lancet 347:845–846PubMedGoogle Scholar
  89. 89.
    Phillips MJ, Ackerley CA, Superina RA, Roberts EA, Filler RM, Levy GA (1996) Excess zinc associated with severe progressive cholestasis in Cree and Ojibwa-Cree children. Lancet 347:866–868PubMedGoogle Scholar
  90. 90.
    Farinati F, Cardin R, de Maria N, Lecis PE, Della Libera G, Burra P, Marafin C, Sturniolo GC, Naccarato R (1995) Zinc, iron, and peroxidation in liver tissue. Cumulative effects of alcohol consumption and virus-mediated damage-a preliminary report. Biol Trace Elem Res 47:193–199PubMedGoogle Scholar
  91. 91.
    Janssens AR, Bosman FT, Ruiter DJ, Van Den Hamer CJ (1984) Immunohistochemical demonstration of the cytoplasmic copper-associated protein in the liver in primary biliary cirrhosis: its identification as metallothionein. Liver 4:139–147PubMedGoogle Scholar
  92. 92.
    Sogawa K, Yamada T, Suzuki Y, Masaki T, Watanabe S, Uchida Y, Arima K, Nishioka M, Matsumoto K (1994) Elevation of ceruloplasmin activity involved in changes of hepatic metal concentration in primary biliary cirrhosis. Res Commun Chem Pathol Pharmacol 84:367–370PubMedGoogle Scholar
  93. 93.
    Ferenci P (1999) Wilson’s disease. Ital J Gastroenterol Hepatol 31:416–425PubMedGoogle Scholar
  94. 94.
    Yuce A, Kocak N, Gurakan F, Ozen H (2000) Wilson’s disease with hepatic presentation in childhood. Indian Pediatr 37:31–36PubMedGoogle Scholar
  95. 95.
    Cuthbert JA (1995) Wilson’s disease: a new gene and an animal model for an old disease. J Investig Med 43:323–336PubMedGoogle Scholar
  96. 96.
    Mulder TP, Janssens AR, Verspaget HW, van Hattum J, Lamers CB (1992) Metallothionein concentration in the liver of patients with Wilson’s disease, primary biliary cirrhosis, and liver metastasis of colorectal cancer. J Hepatol 16:346–350PubMedGoogle Scholar
  97. 97.
    Gill HH, Shankaran K, Desai HG (1994) Wilson’s disease: varied hepatic presentations. Indian J Gastroenterol 13:95–98PubMedGoogle Scholar
  98. 98.
    Ramadori G, Keidl E, Hutteroth T, Dormeyer HH, Manns M, Meyer zum Buschenfelde KH (1985) [Oral zinc in Wilson disease–an alternative to D-penicillamine]. Z Gastroenterol 23:25–29PubMedGoogle Scholar
  99. 99.
    Brewer GJ, Yuzbasiyan-Gurkan V, Lee DY, Appelman H (1989) Treatment of Wilson’s disease with zinc. VI. Initial treatment studies. J Lab Clin Med 114:633–638PubMedGoogle Scholar
  100. 100.
    Brewer GJ (2003) Tetrathiomolybdate anticopper therapy for Wilson’s disease inhibits angiogenesis, fibrosis and inflammation. J Cell Mol Med 7:11–20PubMedGoogle Scholar
  101. 101.
    Zhao M, Matter K, Laissue JA, Zimmermann A (1995) Copper/zinc and manganese superoxide dismutase immunoreactivity in hepatic iron overload diseases. Histol Histopathol 10:925–935PubMedGoogle Scholar
  102. 102.
    Brissot P, Le Treut A, Dien G, Cottencin M, Simon M, Bourel M (1978) Hypovitaminemia A in idiopathic hemochromatosis and hepatic cirrhosis. Role of retinol-binding protein and zinc. Digestion 17:469–478PubMedGoogle Scholar
  103. 103.
    Adams PC, Bradley C, Frei JV (1991) Hepatic zinc in hemochromatosis. Clin Invest Med 14:16–20PubMedGoogle Scholar
  104. 104.
    Grungreiff K, Abicht K, Kluge M, Presser HJ, Franke D, Kleine FD, Klauck S, Diete U (1988) Clinical studies on zinc in chronic liver diseases. Z Gastroenterol 26:409–415PubMedGoogle Scholar
  105. 105.
    Atukorala TM, Herath CA, Ramachandran S (1986) Zinc and vitamin A status of alcoholics in a medical unit in Sri Lanka. Alcohol Alcohol 21:269–275PubMedGoogle Scholar
  106. 106.
    Poschl G, Seitz HK (2004) Alcohol and cancer. Alcohol Alcohol 39:155–165PubMedGoogle Scholar
  107. 107.
    Karayalcin S, Arcasoy A, Uzunalimoglu O (1988) Zinc plasma levels after oral zinc tolerance test in nonalcoholic cirrhosis. Dig Dis Sci 33:1096–1102PubMedGoogle Scholar
  108. 108.
    Ijuin H (1998) Evaluation of pancreatic exocrine function and zinc absorption in alcoholism. Kurume Med J 45:1–5PubMedGoogle Scholar
  109. 109.
    Milman N, Hvid-Jacobsen K, Hegnhoj J, Sorensen SS (1983) Zinc absorption in patients with compensated alcoholic cirrhosis. Scand J Gastroenterol 18:871–875PubMedCrossRefGoogle Scholar
  110. 110.
    Yoshida Y, Higashi T, Nouso K, Nakatsukasa H, Nakamura SI, Watanabe A, Tsuji T (2001) Effects of zinc deficiency/zinc supplementation on ammonia metabolism in patients with decompensated liver cirrhosis. Acta Med Okayama 55:349–355PubMedGoogle Scholar
  111. 111.
    Kahn AM, Ozeran MD (1967) Liver and serum zinc abnormalities in rats with cirrhosis. Gastroenterology 53:193–197Google Scholar
  112. 112.
    Kiilerich S, Christiansen C (1986) Distribution of serum zinc between albumin and alpha 2-macroglobulin in patients with different zinc metabolic disorders. Clin Chim Acta 154:1–6PubMedGoogle Scholar
  113. 113.
    Giroux E, Schechter PJ, Schoun J, Sjoerdsma A (1977) Reduced binding of added zinc in serum of patients with decompensated hepatic cirrhosis. Eur J Clin Invest 7:71–73PubMedCrossRefGoogle Scholar
  114. 114.
    Keeling PW, Ruse W, Bull J, Hannigan B, Thompson RP (1981) Direct measurement of the hepatointestinal extraction of zinc in cirrhosis and hepatitis. Clin Sci (Lond) 61:441–444Google Scholar
  115. 115.
    Prasad AS (2001) Recognition of zinc-deficiency syndrome. Nutrition 17:67–69PubMedGoogle Scholar
  116. 116.
    Prasad AS (2001) Discovery of human zinc deficiency: impact on human health. Nutrition 17:685–687PubMedGoogle Scholar
  117. 117.
    Prasad AS (2003) Zinc deficiency. BMJ 326:409–410PubMedGoogle Scholar
  118. 118.
    Black MM (2003) The evidence linking zinc deficiency with children’s cognitive and motor functioning. J Nutr 133:1473S–1476SPubMedGoogle Scholar
  119. 119.
    Sandstead HH (2000) Causes of iron and zinc deficiencies and their effects on brain. J Nutr 130:347S–349SPubMedGoogle Scholar
  120. 120.
    Prasad AS (1985) Clinical and biochemical manifestations of zinc deficiency in human subjects. J Am Coll Nutr 4:65–72PubMedGoogle Scholar
  121. 121.
    Baskol M, Ozbakir O, Coskun R, Baskol G, Saraymen R, Yucesoy M (2004) The role of serum zinc and other factors on the prevalence of muscle cramps in non-alcoholic cirrhotic patients. J Clin Gastroenterol 38:524–529PubMedGoogle Scholar
  122. 122.
    Kugelmas M (2000) Preliminary observation: oral zinc sulfate replacement is effective in treating muscle cramps in cirrhotic patients. J Am Coll Nutr 19:13–15PubMedGoogle Scholar
  123. 123.
    Maillard H, Celerier P, Maisonneuve C, Forest JL, Blanchi A, Pasquiou C (1995) [Necrolytic migrating erythema without glucagonoma]. Ann Dermatol Venereol 122:786–788PubMedGoogle Scholar
  124. 124.
    Delaporte E, Catteau B, Piette F (1997) Necrolytic migratory erythema-like eruption in zinc deficiency associated with alcoholic liver disease. Br J Dermatol 137:1027–1028PubMedGoogle Scholar
  125. 125.
    Wang LC, Bushey S (2005) Acquired acrodermatitis enteropathica. N Engl J Med 352:1121PubMedGoogle Scholar
  126. 126.
    Sturniolo GC, D’Inca R, Parisi G, Giacomazzi F, Montino MC, D’Odorico A, Soranzo P, Naccarato R (1992) Taste alterations in liver cirrhosis: are they related to zinc deficiency? J Trace Elem Electrolytes Health Dis 6:15–19PubMedGoogle Scholar
  127. 127.
    Madden AM, Bradbury W, Morgan MY (1997) Taste perception in cirrhosis: its relationship to circulating micronutrients and food preferences. Hepatology 26:40–48PubMedGoogle Scholar
  128. 128.
    Prasad AS (1985) Clinical and biochemical manifestation zinc deficiency in human subjects. J Pharmacol 16:344–352PubMedGoogle Scholar
  129. 129.
    Garrett-Laster M, Russell RM, Jacques PF (1984) Impairment of taste and olfaction in patients with cirrhosis: the role of vitamin A. Hum Nutr Clin Nutr 38:203–214PubMedGoogle Scholar
  130. 130.
    Russell RM, Cox ME, Solomons NW (1983) Zinc and special senses. Ann Intern Med 99:227–239PubMedGoogle Scholar
  131. 131.
    Burch RE, Sackin DA, Ursick JA, Jetton MM, Sullivan JF (1978) Decreased taste and smell acuity in cirrhosis. Arch Intern Med 138:743–746PubMedGoogle Scholar
  132. 132.
    Weismann K, Christensen E, Dreyer V (1979) Zinc supplementation in alcoholic cirrhosis. A double-blind clinical trial. Acta Med Scand 205:361–366PubMedCrossRefGoogle Scholar
  133. 133.
    Scholmerich J, Langenberger G, Steiert B, Lohle E, Wokalet H, Tauber R, Kottgen E, Gerok W (1986) Long term zinc substitution in patients with zinc deficiency in liver cirrhosis-results of a placebo controlled trial. Gastroenterology 90:1756Google Scholar
  134. 134.
    Riggio D (1982) Glucose intolerance in liver cirrosis. Metabolism 31:627–634PubMedGoogle Scholar
  135. 135.
    Grungreiff K, Reinhold D (2005) Liver cirrhosis and “liver” diabetes mellitus are linked by zinc deficiency. Med Hypotheses 64:316–317PubMedGoogle Scholar
  136. 136.
    Marchesini G, Bugianesi E, Ronchi M, Flamia R, Thomaseth K, Pacini G (1998) Zinc supplementation improves glucose disposal in patients with cirrhosis. Metabolism 47:792–798PubMedGoogle Scholar
  137. 137.
    Song YM, Chen MD (2003) Zinc supplementation attenuates thioacetamide-induced liver injury and hyperglycemia in mice. Biol Trace Elem Res 92:173–180PubMedGoogle Scholar
  138. 138.
    Marchesini G, Fabbri A, Bianchi G, Brizi M, Zoli M (1996) Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis. Hepatology 23:1084–1092PubMedGoogle Scholar
  139. 139.
    Barry MG, Macmathuna P, Younger K, Keeling PW, Feely J (1991) Effect of zinc supplementation on oxidative drug metabolism in patients with hepatic cirrhosis. Br J Clin Pharmacol 31:488–491PubMedGoogle Scholar
  140. 140.
    Gronbaek K, Friis H, Feldman M, Sonne J, Andreasen PB (1996) Lack of effect of zinc supplementation on antipyrine clearance in alcoholic liver disease. Eur J Clin Pharmacol 49:397–399PubMedGoogle Scholar
  141. 141.
    Cabre M, Camps J, Ferre N, Paternain JL, Joven J (2001) The antioxidant and hepatoprotective effects of zinc are related to hepatic cytochrome P450 depression and metallothionein induction in rats with experimental cirrhosis. Int J Vitam Nutr Res 71:229–236PubMedGoogle Scholar
  142. 142.
    Dhawan D, Goel A (1995) Further evidence for zinc as a hepatoprotective agent in rat liver toxicity. Exp Mol Pathol 63:110–117PubMedGoogle Scholar
  143. 143.
    Quero Guillen JC, Carmona Soria I, Garcia Montes JM, Jimenez Saenz M, Herrerias Gutierrez JM (2003) Hepatic encephalopathy: nomenclature, pathogenesis and treatment. Rev Esp Enferm Dig 95:127–142Google Scholar
  144. 144.
    Katayama K (2004) Ammonia metabolism and hepatic encephalopathy. Hepatol Res 30S:73–80PubMedGoogle Scholar
  145. 145.
    Yang SS, Lai YC, Chiang TR, Chen DF, Chen DS (2004) Role of zinc in subclinical hepatic encephalopathy: comparison with somatosensory-evoked potentials. J Gastroenterol Hepatol 19:375–379PubMedGoogle Scholar
  146. 146.
    Romero-Gomez M, Boza F, Garcia-Valdecasas MS, Garcia E, Aguilar-Reina J (2001) Subclinical hepatic encephalopathy predicts the development of overt hepatic encephalopathy. Am J Gastroenterol 96:2718–2723PubMedGoogle Scholar
  147. 147.
    Van Der Rijt CC, Schalm SW, Schat H, Foeken K, De Jong G (1991) Overt hepatic encephalopathy precipitated by zinc deficiency. Gastroenterology 100:1114–1118PubMedGoogle Scholar
  148. 148.
    Reding P, Duchateau J, Bataille C (1984) Oral zinc supplementation improves chronic encephalopathy. Lancet 19:493–495Google Scholar
  149. 149.
    Nomura F, Takekoshi K (1994) [Zinc and selenium metabolism in liver cirrhosis]. Nippon Rinsho 52:165–169PubMedGoogle Scholar
  150. 150.
    Marchetti P, Amodio P, Caregaro L, Gatta A (1998) [Zinc deficiency in liver cirrhosis: a curiosity or a problem?]. Ann Ital Med Int 13:157–162PubMedGoogle Scholar
  151. 151.
    Riggio O, Ariosto F, Merli M, Caschera M, Zullo A, Balducci G, Ziparo V, Pedretti G, Fiaccadori F, Bottari E, et al. (1991) Short-term oral zinc supplementation does not improve chronic hepatic encephalopathy. Results of a double-blind crossover trial. Dig Dis Sci 36:1204–1208PubMedGoogle Scholar
  152. 152.
    Bresci G, Parisi G, Banti S (1993) Management of hepatic encephalopathy with oral zinc supplementation: a long-term treatment. Eur J Med 2:414–416PubMedGoogle Scholar
  153. 153.
    Grungreiff K, Presser HJ, Franke D, Lossner B, Abicht K, Kleine FD (1989) Correlations between zinc, amino acids and ammonia in liver cirrhosis. Z Gastroenterol 27:731–735PubMedGoogle Scholar
  154. 154.
    Ariosto F, Riggio O, Cantafora A, Colucci S, Gaudio E, Mechelli C, Merli M, Seri S, Capocaccia L (1989) Carbon tetrachloride-induced experimental cirrhosis in the rat: a reappraisal of the model. Eur Surg Res 21:280–286PubMedGoogle Scholar
  155. 155.
    Riggio O, Merli M, Capocaccia L, Caschera M, Zullo A, Pinto G, Gaudio E, Franchitto A, Spagnoli R, D’Aquilino E, et al. (1992) Zinc supplementation reduces blood ammonia and increases liver ornithine transcarbamylase activity in experimental cirrhosis. Hepatology 16:785–789PubMedGoogle Scholar
  156. 156.
    Aquilio E, Spagnoli R, Riggio D, Seri S (1993) Effects of zinc on hepatic ornithine transcarbamylase (OTC) activity. J Trace Elem Electrolytes Health Dis 7:240–241PubMedGoogle Scholar
  157. 157.
    Camps J, Bargallo T, Gimenez A, Alie S, Caballeria J, Pares A, Joven J, Masana L, Rodes J (1992) Relationship between hepatic lipid peroxidation and fibrogenesis in carbon tetrachloride-treated rats: effect of zinc administration. Clin Sci (Lond) 83:695–700Google Scholar
  158. 158.
    Kojima-Yuasa A, Ohkita T, Yukami K, Ichikawa H, Takami N, Nakatani T, Opare Kennedy D, Nishiguchi S, Matsui-Yuasa I (2003) Involvement of intracellular glutathione in zinc deficiency-induced activation of hepatic stellate cells. Chem Biol Interact 146:89–99PubMedGoogle Scholar
  159. 159.
    Dashti HM, Mathew TC, Jadaon MM, Ashkanani E (1997) Zinc and liver cirrhosis: biochemical and histopathologic assessment. Nutrition 13:206–212PubMedGoogle Scholar
  160. 160.
    Takahara T, Furui K, Funaki J, Nakayama Y, Itoh H, Miyabayashi C, Sato H, Seiki M, Ooshima A, Watanabe A (1995) Increased expression of matrix metalloproteinase-II in experimental liver fibrosis in rats. Hepatology 21:787–795PubMedCrossRefGoogle Scholar
  161. 161.
    Anttinen H, Ryhanen L, Puistola U, Arranto A, Oikarinen A (1984) Decrease in liver collagen accumulation in carbon tetrachloride-injured and normal growing rats upon administration of zinc. Gastroenterology 86:532–539PubMedGoogle Scholar
  162. 162.
    Gimenez A, Pares A, Alie S, Camps J, Deulofeu R, Caballeria J, Rodes J (1994) Fibrogenic and collagenolytic activity in carbon-tetrachloride-injured rats: beneficial effects of zinc administration. J Hepatol 21:292–298PubMedGoogle Scholar
  163. 163.
    Loguercio C, De Girolamo V, Federico A, Feng SL, Crafa E, Cataldi V, Gialanella G, Moro R, Del Vecchio Blanco C (2001) Relationship of blood trace elements to liver damage, nutritional status, and oxidative stress in chronic nonalcoholic liver disease. Biol Trace Elem Res 81:245–254PubMedGoogle Scholar
  164. 164.
    Cabre M, Camps J, Paternain JL, Ferre N, Joven J (2000) Time-course of changes in hepatic lipid peroxidation and glutathione metabolism in rats with carbon tetrachloride-induced cirrhosis. Clin Exp Pharmacol Physiol 27:694–699PubMedGoogle Scholar
  165. 165.
    Sullivan JF, Jetton MM, Hahn HK, Burch RE (1980) Enhanced lipid peroxidation in liver microsomes of zinc-deficient rats. Am J Clin Nutr 33:51–56PubMedGoogle Scholar
  166. 166.
    Chvapil M, Ryan JN, Elias SL, Peng YM (1973) Protective effect of zinc on carbon tetrachloride-induced liver injury in rats. Exp Mol Pathol 19:186–196PubMedGoogle Scholar
  167. 167.
    Ferre N, Girona J, Cabre M, Joven J, LaVille A, Masana L, Paternain JL, Camps J (1999) Hepatic production of apolar aldehydes in rats with carbon tetrachloride-induced cirrhosis. Mol Cell Biochem 198:57–60PubMedGoogle Scholar
  168. 168.
    Abul HT, Mathew TC, Abul F, Al-Sayer H, Dashti HM (2002) Antioxidant enzyme level in the testes of cirrhotic rats. Nutrition 18:56–59PubMedGoogle Scholar
  169. 169.
    Liaw KY, Lee PH, Wu FC, Tsai JS, Lin-Shiau SY (1997) Zinc, copper, and superoxide dismutase in hepatocellular carcinoma. Am J Gastroenterol 92:2260–2263PubMedGoogle Scholar
  170. 170.
    Gerli G, Locatelli GF, Mongiat R, Zenoni L, Agostoni A, Moschini G, Zafiropoulos D, Bruno S, Rossi S, Vignati A, et al. (1992) Erythrocyte antioxidant activity, serum ceruloplasmin, and trace element levels in subjects with alcoholic liver disease. Am J Clin Pathol 97:614–618PubMedGoogle Scholar
  171. 171.
    Zhao M, Matter K, Laissue JA, Zimmermann A (1996) Copper/zinc and manganese superoxide dismutases in alcoholic liver disease: immunohistochemical quantitation. Histol Histopathol 11:899–907PubMedGoogle Scholar
  172. 172.
    Abul H, Mathew TC, Dashti H, Al-Bader A (2002) Level of superoxide dismutase, gloutathione peroxidase and uric acid in thioacetamide-induced cirrhotic rats. Anat Histol Embryol 31:66–71PubMedGoogle Scholar
  173. 173.
    Behbehani A, Dashti H, Simsek M, Lari A, Al-Adnani M (1992) The role of zinc sulphate in normalizing superoxide dismutase activity in experimental liver cirrhosis. Surg Res Comm 11:261–269Google Scholar
  174. 174.
    Sato S, Shimizu M, Hosokawa T, Saito T, Okabe M, Niioka T, Kurasaki M (2000) Distribution of zinc-binding metallothionein in cirrhotic liver of rats administered zinc. Pharmacol Toxicol 87:292–296PubMedGoogle Scholar
  175. 175.
    Cai L, Wang GJ, Xu ZL, Deng DX, Chakrabarti S, Cherian MG (1998) Metallothionein and apoptosis in primary human hepatocellular carcinoma (HCC) from northern China. Anticancer Res 18:4667–4672PubMedGoogle Scholar
  176. 176.
    Nakayama A, Fukuda H, Ebara M, Hamasaki H, Nakajima K, Sakurai H (2002) A new diagnostic method for chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma based on serum metallothionein, copper, and zinc levels. Biol Pharm Bull 25:426–431PubMedGoogle Scholar
  177. 177.
    Kim CH, Kim JH, Lee J, Ahn YS (2003) Zinc-induced NF-kappaB inhibition can be modulated by changes in the intracellular metallothionein level. Toxicol Appl Pharmacol 190:189–196PubMedGoogle Scholar
  178. 178.
    Ho E, Quan N, Tsai YH, Lai W, Bray TM (2001) Dietary zinc supplementation inhibits NF-kappaB activation and protects against chemically induced diabetes in CD1 mice. Exp Biol Med 226:103–111Google Scholar
  179. 179.
    Eng FJ, Friedman SL (2001) Transcriptional regulation in hepatic stellate cells. Semin Liver Dis 21:385–395PubMedGoogle Scholar
  180. 180.
    Ho E, Ames BN (2002) Low intracellular zinc induces oxidative DNA damage, disrupts NF-kappaB and AP1 DNA binding and affects DNA repair in glioma cell line. Proc Natl Acad Sci USA 99:16770–16775PubMedGoogle Scholar
  181. 181.
    Prasad AS, Bao B, Beck FW, Sarkar FH (2002) Zinc enhances the expression of interleukin-2 and interleukin-2 receptors in HUT-78 cells by way of NF-kappaB activation. J Lab Clin Med 140:272–289PubMedGoogle Scholar
  182. 182.
    Oteiza PI, Clegg MS, Keen CL (2001) Short-term zinc deficiency affects nuclear factor-kappab nuclear binding activity in rat testes. J Nutr 131:21–26PubMedGoogle Scholar
  183. 183.
    Zarski JP, 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 11:856–860PubMedGoogle Scholar
  184. 184.
    Weismann K, Hoyer H, Christensen E (1980) Acquired zinc deficiency in alcoholic liver cirrhosis: report of two cases. Acta Derm Venereol 60:447–449PubMedGoogle Scholar
  185. 185.
    Labadie H, Verneau A, Trinchet JC, Beaugrand M (1986) [Does oral zinc improve the cellular immunity of patients with alcoholic cirrhosis?]. Gastroenterol Clin Biol 10:799–803PubMedGoogle Scholar
  186. 186.
    Jiang Z, You DY, Chen XC, Wu J (1992) Monitoring of serum markers for fibrosis during CCl4-induced liver damage. Effects of anti-fibrotic agents. J Hepatol 16:282–289PubMedGoogle Scholar
  187. 187.
    Gaudio E, Pannarale L, Franchitto A, Riggio O (1993) Zinc supplementation in experimental liver cirrhosis: a morphological, structural and ultrastructural study. Int J Exp Pathol 74:463–469PubMedGoogle Scholar
  188. 188.
    Saldeen T (1969) On the protective action of zinc against experimental liver damage due to choline free diet or carbon tetrachloride. Z Gesamte Exp Med 150:251–259PubMedGoogle Scholar
  189. 189.
    Ebara M, Fukuda H, Hatano R, Yoshikawa M, Sugiura N, Saisho H, Kondo F, Yukawa M (2003) Metal contents in the liver of patients with chronic liver disease caused by hepatitis C virus. Reference to hepatocellular carcinoma. Oncology 65:323–330PubMedGoogle Scholar
  190. 190.
    Frezza EE, Gerunda GE, Farinati F, Plebani M, Giacomin A, Galligioni A, Neri D, Merenda R, Toniolo E, De Maria N, et al. (1993) Sex hormones and trace elements in rat CCL4-induced cirrhosis and hepatocellular carcinoma. Eur J Cancer Prev 2:357–359PubMedGoogle Scholar
  191. 191.
    Frezza EE, Gerunda GE, Farinati F, DeMaria N, Galligioni A, Plebani F, Giacomin A, Van Thiel DH (1994) CCL4-induced liver cirrhosis and hepatocellular carcinoma in rats: relationship to plasma zinc, copper and estradiol levels. Hepatogastroenterology 41:367–369PubMedGoogle Scholar
  192. 192.
    Nagasue N, Kolno H, Chang YC, Nakamura T (1989) Iron, copper and zinc levels in serum and cirrhotic liver of patients with and without hepatocellular carcinoma. Oncology 46:293–296PubMedCrossRefGoogle Scholar
  193. 193.
    Poo JL, Rosas-Romero R, Montemayor AC, Isoard F, Uribe M (2003) Diagnostic value of the copper/zinc ratio in hepatocellular carcinoma: a case control study. J Gastroenterol 38:45–51PubMedGoogle Scholar
  194. 194.
    Shang YJ, Zhao DH, Huang CX (1994) Changes in serum copper levels and its clinical significance in patients with cirrhosis and hepatocellular carcinoma. Clin J Int Med 33:113–116Google Scholar
  195. 195.
    Kollmeier H, Seemann J, Wittig P, Rothe G, Witting C (1992) Zinc concentrations in human tissues. Liver zinc in carcinoma and severe liver disease. Pathol Res Pract 188:942–945PubMedGoogle Scholar
  196. 196.
    Shimizu I, Inoue H, Yano M, Shinomiya H, Wada S, Tsuji Y, Tsutsui A, Okamura S, Shibata H, Ito S (2001) Estrogen receptor levels and lipid peroxidation in hepatocellular carcinoma with hepatitis C virus infection. Liver 21:342–349PubMedGoogle Scholar
  197. 197.
    Inagaki T, Katoh K, Takiya S, Ikuta K, Kobayashi S, Suzuki M, Fukuzawa Y, Ayakawa T, Shimizu K, Tagaya T, et al. (1992) Relationship between superoxide dismutase (SOD) and viral liver disease. Gastroenterol Jpn 27:382–389PubMedGoogle Scholar
  198. 198.
    Borrello S, De Leo ME, Wholrab H, Galeotti T (1992) Manganese deficiency and transcriptional regulation of mitochondrial superoxide dismutase on hepatomas. FEBS Lett 310:249–254PubMedGoogle Scholar
  199. 199.
    Borello S, De Leo ME, Galeotti T (1993) Defective gene expression of Mn SOD in cancer cells. Mol Aspects Med 14:253–258Google Scholar
  200. 200.
    Orlando R, Tosone G, De Fino M, Cangiano F (1987) [Changes in the levels of serum zinc in chronic hepatopathy]. Minerva Med 78:1759–1763PubMedGoogle Scholar
  201. 201.
    Solis-Herruzo J, De Cuenca B, Munoz-Rivero MC (1989) Intestinal zinc absorption in cirrhotic patients. Z Gastroenterol 27:335–338PubMedGoogle Scholar
  202. 202.
    Sartori M, Calgaro M, Campanini M, Carnevale Schianca GP, De Simone GG, Dugnani M, Pozzoli G (1988) [Determination of zinc and copper in patients with liver cirrhosis of diverse clinical severity]. Minerva Med 79:891–895PubMedGoogle Scholar
  203. 203.
    Allan JG, Fell GS, Russell RI (1975) Urinary zinc in hepatic cirrhosis. Scott Med J 20:109–111PubMedGoogle Scholar
  204. 204.
    Gusau KA, Elegbede JA, Idoko JA, Wali SS (1990) Zinc status in chronic liver disease; studies in Nigerian patients. West Afr J Med 9:245–251PubMedGoogle Scholar
  205. 205.
    Goksu N, Ozsoylu S (1986) Hepatic and serum levels of zinc, copper, and magnesium in childhood cirrhosis. J Pediatr Gastroenterol Nutr 5:459–462PubMedCrossRefGoogle Scholar
  206. 206.
    Loyke HF (1984) Copper and zinc in CCl4 treated rats. Bull Environ Contam Toxicol 32:405–409PubMedGoogle Scholar
  207. 207.
    Minami T, Matsuda H, Kubo M, Okazaki Y (1986) Trace elements (Cu, Fe, Zn) in several tissues of CCl4-induced chronic hepatitis rats. Bull Environ Contam Toxicol 36:306–310PubMedGoogle Scholar
  208. 208.
    Dashti H, Jeppsson B, Hagerstrand I, Hultberg B, Srinivas U, Abdulla M, Bengmark S (1989) Thioacetamide-and carbon tetrachloride-induced liver cirrhosis. Eur Surg Res 21:83–91PubMedGoogle Scholar
  209. 209.
    Dashti HM, Al-Sayer H, Behbehani A, Madda J, Christenson JT (1992) Liver cirrhosis induced by carbon tetrachloride and the effect of superoxide dismutase and xanthine oxidase inhibitor treatment. J R Coll Surg Edinb 37:23–28PubMedGoogle Scholar
  210. 210.
    Al-Bader A, Mathew TC, Khoursheed M, Asfar S, Al-Sayer H, Dashti HM (2000) Thioacetamide toxicity and the spleen: histological and biochemical analysis. Anat Histol Embryol 29:3–8PubMedGoogle Scholar
  211. 211.
    Al-Bader A, Mathew TC, Abul H, Al-Mosawi M, Dashti H, Kumar D, Singal PK (1999) Thioacetamide induced changes in trace elements and kidney damage. J Trace Elem Exp Med 12:1–14Google Scholar
  212. 212.
    Al-Bader AA, Mosawi MH, Hussain TA, Dashti HM (1997) Effect of dietary selenium, zinc and allopurinol supplements on plasma and tissue manganese levels in rats with thioacetamide [correction of thiocetamide]-induced liver cirrhosis. Mol Cell Biochem 173:121–125PubMedGoogle Scholar
  213. 213.
    Dashti H, Jeppsson B, Abdulla M, Srinivas U, Hagerstrand I, Bengmark S (1986) Changes in the plasma levels of copper, zinc, calcium, magnesium and selenium in thioacetamide induced liver cirrhosis. Acta Pharmacol Toxicol (Copenh) 59(Suppl 7):219–222Google Scholar
  214. 214.
    Loguercio C, De Girolamo V, Federico A, Feng SL, Cataldi V, Del Vecchio Blanco C, Gialanella G (1997) Trace elements and chronic liver diseases. J Trace Elem Med Biol 11:158–161PubMedGoogle Scholar
  215. 215.
    Ko WS, Guo CH, Yeh MS, Lin LY, Hsu GS, Chen PC, Luo MC, Lin CY (2005) Blood micronutrient, oxidative stress, and viral load in patients with chronic hepatitis C. World J Gastroenterol 11:4697–4702PubMedGoogle Scholar
  216. 216.
    Gaveau D, Piette F, Cortot A, Dumur V, Bergoend H (1987) [Cutaneous manifestations of zinc deficiency in ethylic cirrhosis]. Ann Dermatol Venereol 114:39–53PubMedGoogle Scholar
  217. 217.
    Schlienger JL, Willemin B, Lang JM, North ML, Simon C, Doffoel M, Bockel R (1986) [Evaluation of malnutrition and immunity in alcoholic liver diseases]. Presse Med 15:1023–1027PubMedGoogle Scholar
  218. 218.
    Bro S, Stokholm M, Jorgensen PJ (1989) Zinc in mononuclear leucocytes in alcoholics with liver cirrhosis or chronic pancreatitis and in patients with Crohn’s disease before and after zinc supplementation. J Trace Elem Electrolytes Health Dis 3:243–248PubMedGoogle Scholar
  219. 219.
    Aaseth J, Smith-Kielland A, Thomassen Y (1986) Selenium, alcohol and liver diseases. Ann Clin Res 18:43–47PubMedGoogle Scholar
  220. 220.
    Vallee BL, Wacker WE, Bartholomay AF, Hoch FL (1957) Zinc metabolism in hepatic dysfunction. II. Correlation of metabolic patterns with biochemical findings. N Engl J Med 257:1055–1065PubMedCrossRefGoogle Scholar
  221. 221.
    Chapman KM, Prabhudesai M, Erdman JW Jr (1993) Vitamin A status of alcoholics upon admission and after two weeks of hospitalization. J Am Coll Nutr 12:77–83PubMedGoogle Scholar
  222. 222.
    Ward RJ, Peters TJ (1992) The antioxidant status of patients with either alcohol-induced liver damage or myopathy. Alcohol Alcohol 27:359–365PubMedGoogle Scholar
  223. 223.
    Valberg LS, Flanagan PR, Ghent CN, Chamberlain MJ (1985) Zinc absorption and leukocyte zinc in alcoholic and nonalcoholic cirrhosis. Dig Dis Sci 30:329–333PubMedGoogle Scholar
  224. 224.
    Mills PR, Fell GS, Bessent RG, Nelson LM, Russell RI (1983) A study of zinc metabolism in alcoholic cirrhosis. Clin Sci (Lond) 64:527–535Google Scholar
  225. 225.
    Rodriguez-Moreno F, Gonzalez-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 14:39–44PubMedGoogle Scholar
  226. 226.
    Milman N, Laursen J, Podenphant J, Asnaes S (1986) Trace elements in normal and cirrhotic human liver tissue. I. Iron, copper, zinc, selenium, manganese, titanium and lead measured by X-ray fluorescence spectrometry. Liver 6:111–117PubMedGoogle Scholar
  227. 227.
    Gonzalez-Reimers E, Rodriguez-Moreno F, Castro-Aleman V, Santolaria-Fernandez F, Galindo-Martin L, Ferres-Torres R, Conde-Martell A (1990) Effect of ethanol on hepatic iron, copper, zinc and manganese contents in the male albino mouse. Drug Alcohol Depend 26:195–198PubMedGoogle Scholar
  228. 228.
    Conde-Martel A, Gonzalez-Reimers E, Santolaria-Fernandez F, Castro-Aleman V, Galindo-Martin L, Rodriguez-Moreno F, Martinez-Riera A (1992) Combined effects of ethanol and protein deficiency on hepatic iron, zinc, manganese, and copper contents. Alcohol 9:341–348PubMedGoogle Scholar
  229. 229.
    Gonzalez-Reimers E, Santolaria-Fernandez F, Perez-Labajos J, Rodriguez-Moreno F, Martinez-Riera A, Hernandez-Torres O, Valladares-Parrilla F, Molina-Perez M (1996) Relative and combined effects of propylthiouracil, ethanol and protein deficiency on liver histology and hepatic iron, zinc, manganese and copper contents. Alcohol Alcohol 31:535–545PubMedGoogle Scholar
  230. 230.
    Gohshi K, Fujiyama S, Shibata J, Sato T, Higashi A, Matsuda I (1995) Zinc absorption and its correlation with results of oral zinc tolerance testing in nonalcoholic liver cirrhosis; kinetic study. Hepatogastroenterology 42:487–491PubMedGoogle Scholar
  231. 231.
    Scholmerich J, Krauss E, Wietholtz H, Kottgen E, Lohle E, Gerok W (1987) Bioavailability of zinc from zinc-histidine complexes. II. Studies on patients with liver cirrhosis and the influence of the time of application. Am J Clin Nutr 45:1487–1491PubMedGoogle Scholar
  232. 232.
    Arakawa Y, Suzuki K, Oyama R, Moriyama M (1996) [Methods and clinical significance of an oral tolerance test of essential trace element, especially an oral zinc tolerance test]. Nippon Rinsho 54:162–171PubMedGoogle Scholar
  233. 233.
    Ferre N, Camps J, Cabre M, Paul A, Joven J (2001) Hepatic paraoxonase activity alterations and free radical production in rats with experimental cirrhosis. Metabolism 50:997–1000PubMedGoogle Scholar
  234. 234.
    Vanaja R, Gajalakshmi BS (1993) Zinc counteracts experimen-tally-induced cirrhotic changes in rats. Indian J Physiol Pharmacol 37:163–164PubMedGoogle Scholar
  235. 235.
    Chvapil M, Ryan JN, Elias SL, Peng YM (1973) Protective effect of zinc on carbon tetrachloride-induced liver injury in rats. Exp Mol Pathol 19:186–196PubMedGoogle Scholar
  236. 236.
    Gimenez A, Caballeria J, Pares A, Alie S, Deulofeu R, Andreu H, Rodes J (1992) Influence of dietary zinc on hepatic collagen and prolyl hydroxylase activity in alcoholic rats. Hepatology 16:815–819PubMedGoogle Scholar
  237. 237.
    Al-Bader AA, Mathew TC, Abul H, Al-Mosawi M, Panigrahi D, Dashti H (1998) Bacterial translocation in thioacetamide induced liver cirrhosis in rats. J R Coll Surg Edinb 43:278–282PubMedGoogle Scholar
  238. 238.
    Dashti H, Abul F, Behbehani A, Hussain T, Madda J (1996) Interleukin-8 and trace elements in experimental liver cirrhosis. J Trace Elem Exper 9:27–40Google Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Ioannis Stamoulis
    • 1
    • 2
  • Grigorios Kouraklis
    • 2
  • Stamatios Theocharis
    • 1
  1. 1.Department of Forensic Medicine and ToxicologyUniversity of Athens, Medical SchoolAthensGreece
  2. 2.2nd Department of Propedeutic SurgeryLaikon General Hospital, University of Athens, Medical SchoolAthensGreece

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