2016, Number 1
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Ann Hepatol 2016; 15 (1)
The role of zinc in liver cirrhosis
Grüngreiff K, Reinhold D, Wedemeyer H
Language: English
References: 101
Page: 7-16
PDF size: 169.18 Kb.
ABSTRACT
Zinc is an essential trace element playing fundamental roles in cellular metabolism. It acts mostly by binding a wide range of proteins,
thus affecting a broad spectrum of biological processes, which include cell division, growth and differentiation. Zinc is critical to a
large number of structural proteins, enzymatic processes, and transcription factors. Zinc deficiency can result in a spectrum of clinical
manifestations, such as poor of appetite, loss of body hair, altered taste and smell, testicular atrophy, cerebral and immune dysfunction,
and diminished drug elimination capacity. These are common symptoms in patients with chronic liver diseases, especially
liver cirrhosis. The liver is the main organ responsible for the zinc metabolism which can be affected by liver diseases. On the other
hand, zinc deficiency may alter hepatocyte functions and also immune responses in inflammatory liver diseases. Liver cirrhosis represents
the most advanced stage of chronic liver diseases and is the common outcome of chronic liver injury. It is associated with
energy malnutrition, with numerous metabolic disorders, such as hypoalbuminemia, with imbalance between branched-chain amino
acids and aromatic amino acids, and with reduced zinc serum concentrations. All these processes can influence the clinical outcome
of patients, such ascites, hepatic encephalopathy and hepatocellular carcinoma. In the present review, we summarize the emerging
evidence on the pitoval role of zinc in the pathogenesis of liver cirrhosis.
REFERENCES
Leoni G, Rosato A, Perozzi G. Zinc proteome interaction network as a model to identify nutrient-affected pathways in human pathologies. Genes Nutr 2014; 9: 436.
Maret W. Zinc in Human Disease. Met Ions Life Sci 2013; 13: 389-414.
Rink L, Haase H. Zinc homeostasis and immunity. Trends Immunol 2007; 28: 1-4.
Brown KH, Wuehler SE. Zinc and Human Health: The Results of Recent Trials and Implications for Program Interventions and Research, Ottawa: Micronutrient Initiative; 2000, p. 1-69.
World Health Report 2002. Reducing Risks, Promoting Healthy Life. Geneva: WHO; 2002, p. 1-250.
Grüngreiff K, Reinhold D. Zinc and Liver. In: Rink L (ed.) Zinc in Human Health. 1st ed. Amsterdam: IOS Press; 2011, p. 473-92.
Maret W. Zinc and sulphur: A critical partnership. Biochemistry 2004; 43: 3301-9.
Stehben WE. Oxidative stress, toxic hepatitis and antioxidants with particular emphasis on zinc. Exp Mol Pathol 2003; 75: 265-76.
Powell SR. The antioxidant properties of zinc. Nutr 2000; 130: 1447S-1454S.
Grüngreiff K, Reinhold D. Zink: Bedeutung in der ärztlichen Praxis. Heßdorf-Klebheim: J. Hartmann Verlag; 2007, p. 1-96.
Buchinger W, Leopold B, Lind P, Langsteger W, Klima G, Koltringer P, Waschnick O, et al. Veränderungen des Zinkspiegels im Serum, Vollblut und im Erythrozyten bei Schilddrüsenstoffwechselstörungen. Wien Klin Wochenschr 1988; 100: 619-21.
Faure P, Roussel M, Richard JM, Foulon T, Groslambert P, Hadijan A, Favier A. Effect of acute zinc depletion on rat lipoprotein distribution and peroxidation. Biol Trace Elem Res 1991; 28: 135-45.
Köttgen E, Büchsel R. Zink und Vitamin A. Z Allg Med 1984; 60: 1043-8.
Prasad AS. Discovery of human zinc deficiency and studies in an experimental human model. Am J Clin Med 1991; 53: 403-12.
Danscher G, Stoltenberg M. Zinc-specific autometallographic in vivo selenium methods: tracing of zinc-enriched (ZEN) terminals, ZEN pathways, and pools of zinc ions in a multitude of other ZEN cells. Cytochem Histochem 2005; 53: 141-53.
Fukada F, Yamasaki S, Nishida K, Murakami, Hirano J. Zinc homeostasis and signaling in health and diseases. J Biol Inorg Chem 2011; 16: 1123-34.
Rink L. Introduction-Why Investigate Zinc? In: Rink L. (ed.). Zinc in Human Health. 1st ed. Amsterdam: IOS Press; 2011, p. 3-6.
Grüngreiff K. Zinc and Liver. Freiburg: Dr. Falk Pharma GmbH; 2013, p. 1-84.
Huber KL, Hardy JA. Mechanism of zinc-mediated inhibition of caspase-9. ProteinSci 2012; 21: 1056-65.
Beyersmann D, Haase H. Functions of zinc in signaling, proliferation and differentiation of mammalian cells. BioMetals 2001; 14: 331-41.
Maret W. Zinc coordination environments in proteins as redox sensors and signal transducers. Antioxid Redox Signal 2006; 8: 1419-41.
Maret W. Human Zinc Biochemistry. In: Rink L (ed.). Zinc in Human Health. 1st ed. Amsterdam: IOS Press; 2011, p. 45-62.
Cousins RJ, Lichten LA. Zinc transporters. In: Rink L (ed.). Zinc in Human Health. 1st ed. Amsterdam: IOS Press; 2011, p. 163-94.
Liuzzi JP, Cousins RJ. Mammalian zinc transporters. Annu Rev Nutr 2004; 24: 151-72.
Lichten LA, Cousins RJ. Mammalian zinc transporters: nutritional and physiologic regulation. Annu Rev Nutr 2009; 29: 153-76.
Maret W. Metals on the move: zinc ions in cellular regulation and in the coordination dynamics of zinc proteins. BioMetals 2011; 24: 411-8.
Foster M, Hancock D, Petocz P, Samman S. Zinc transporter genes are coordinately expressed in men and women independently of dietary or plasma zinc. J Nutr 2011; 141: 1195- 201.
Ho E. Zinc deficiency, DNA damage and cancer risk. J Nutr Biochem 2004; 15: 572-8.
Tuerk MJ, Fazel N. Zinc deficiency. Curr Opin Gastroenterol 2009; 25: 136-43.
Taylor JA, Simmons TJB. The mechanisms of zinc uptake by cultured rat liver cells. J Physiol 1994; 474: 55-60.
Cousins RJ. Absorption, transport, and hepatic metabolism of copper and zinc: special reference to metallothionein and ceruloplasmin. Physiol Rev 1985; 65: 238-309.
tom Dieck H, Doring F, Roth HP, Daniel H. Changes in rat hepatic gene expression in response to zinc deficiency as assessed by DNA arrays. J Nutr 2003; 133: 1004-10.
Liuzzi JP, Lichten LA, Rivera S, Blanchard RK, Aydemir TB, Knutson MD, Ganz T, et al. Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc Natl Acad Sci 2005; 102: 6843-48.
Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 2004; 306: 2090-93.
Hentze MW, Muckenthaler MU, Andrews NC. Balancing acts: molecular control of mammalian iron metabolism. Cell 2004; 117: 285-97.
Aydemir TB, Sitren HS, Cousins RJ. The Zinc Transporter zip 14 Influences c-Met Phosphorylation and Hepatocyte Proliferation during Liver Regeneration in Mice. Gastroenterology 2012; 142: 1536-46.
Franklin RB, Levy BA, Zou J, Hanna N, Desouki MM, Bagasra O, Johnson LA, et al. ZIP14 zinc transporter down regulation and zinc depletion in the development and progression of hepatocellular cancer. J Gastrointest Cancer 2012; 43: 249-57.
Cuthberson DP, Fell GS, Smith CM, Tilstone WJ. Metabolism after injury. 1. Effects of severity, nutrition and enviromental temperature on protein, potassium, zinc, and creatine. Br J Surg 1972; 59: 925-31.
Barry M, Keeling PWN, Feely J. Tissue zinc status and drug elimination in patients with chronic liver disease. Clin Sci 1990; 78: 547-51.
Oteiza PI, Mackenzie GG. Zinc, oxidant-triggered cell signalling, and human health. Mol Aspects Med 2005; 26: 245-55.
DiSilvestro RA. Zinc in relation to diabetes and oxidative disease. J Nutr 2000; 130: 1509S-1511S.
Parsons SE, Di Silvestro RA. Effects of mild zinc deficiency, plus or minus an acute-phase response on galactosamineinduced hepatitis in rats. Br Nutr 1994; 72: 611-8.
Mohammad MK, Zhou Z, Cave M, Barve A, McClain CJ. Zinc and Liver Disease. Nutr Clin Pract 2012; 27: 8-20.
Gaetke L, McClain CL, Talwalkar R, Shedlowski S. Effects of endotoxin on zinc metabolism in human volunteers. Am Physiol 1997; 272: E952-E956.
McClain CL, McClain ML, Boosalis MG, Hennig B. Zinc in the stress response. Scand J Work Environ Health 1993; 19: 132-33.
Albillos A, Lario M, Alvarez-Mon M. Cirrhosis-associated immune dysfunction: Distinctive features and clinical relevance. J Hepatol 2014; 61: 1385-96.
Jenne CN, Kubes P. Immune surveillance by the liver. Nat Immunol 2013; 4: 996-1006.
Racanelli V, Rehermann B. The liver as an immunological organ. Hepatology 2006; 43: S54-S62.
Wiest R, Lawson M, Geuking M. Pathological translocation in liver cirrhosis. J Hepatol 2014; 60: 197-209.
Amodio P, Bémeur C, Butterworth R, Cordoba J, Kato A, Montagnese S, Uribe M, et al. The nutritional management of hepatic encephalopathy in patients with cirrhosis: International Society for Hepatic Encephalopathy and Nitrogen Metabolism Consensus. Hepatology 2013; 58: 325-36.
Bémeur C, Desjardins P, Butterworth RF. Role of nutrition in the management of hepatic encephalopathy in end-stage liver failure. J Nutr Metab 2010; 2010: ID489823.
O’Brien A, Williams R. Nutrition in end-stage liver disease: principles and practice. Gastroenterology 2008; 134: 1729-40.
Grüngreiff K, Presser HJ, Franke D, Lössner B, Abicht K, Kleine FD. Correlations between zinc, amino acids and ammonia in liver cirrhosis. Z Gastroenterol 1989; 27: 731-5.
Buchman AL. Total parenteral nutrition: challenges and practice in the cirrhotic patient. Transplant Proc 2006; 38: 1659-63.
Hayashi M, Ikezawa K, Ono A, Okabayashi S, Hayashi Y, Shimizu S, Mizuno T, et al. Evaluation of the effects of combination therapy with branched-chain amino acid and zinc supplements on nitrogen metabolism in liver cirrhosis. Hepatol Res 2007; 37: 615-9.
Itou M, Kawaguchi T, Taniguchi E, Oku Y, Fukushima N, Ando E, Oriishi T, et al. Branched-chain amino acid supplements reduced ascites and increased the quality of life in a patient with liver cirrhosis: A case report. Mol Med Rep 2009; 2: 977-81.
Bianchi G, Marzocchi R, Lorusso C, Ridolfi V, Marchesini G. Nutritional treatment of chronic liver failure. Hepatol Res 2008; 38: 93-101.
Garcia-Martinez R, Caraceni P, Bernardi M, Gines P, Arroyo V, Jalan R. Albumin: pathophysiologic basis of its role in the treatment of cirrhosis and its complications. Hepatology 2013; 58: 1836-46.
Bal W, Soko³owska M, Kurowska E, Faller P. Binding of transition metal ions to albumin: sites, affinities and rates. Biochim Biophys Acta 2013; 1830: 5444-55.60. Lu J, Stewart AJ, Sadler PJ, Pinheiro TJ, Blindauer CA. Albumin as a zinc carrier: properties of its high-affinity zinc-binding site. Biochem Soc Trans 2008; 36: 1317-21.
Cousins RJ. Toward a molecular understanding of zinc metabolism. Clin Physiol Biochem 1986; 4: 20-30.
Grüngreiff K, Franke D, Lössner B, Abicht K, Kleine FD. Zinc deficiency-A factor in the pathogenesis of hepatic encephalopathy. Z Gastroenterol 1991; 29: 101-6.
Tajiri K, Shimizu Y. Branched-chain amino acids in liver diseases. World J Gastroenterol 2013; 19: 7620-9.
Holecek M. Branched-chain amino acids and ammonia metabolism in liver disease: therapeutic implications. Nutrition 2013; 29: 1186-91.
Hara K, Yonezawa K, Weng QP, Kozlowski MT, Belham C, Avruch J. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol Chem 1998; 273: 14484-94.
Kuwahata M, Kubota H, Katsukawa M, Ito S, Ogawa A, Kobayashi Y, Nakamura Y, et al. Effect of branched-chain amino acid supplementation on the oxidized/reduced state of plasma albumin in rats with chronic liver disease. J Clin Biochem Nutr 2012; 50: 67-71.
Takuma Y, Nouso K, Makino Y, Hayashi M, Takahashi H. Clinical trial: oral zinc in hepatic encephalopathy. Aliment Pharmacol Ther 2010; 32: 1080-90.
Padula G, Gonzalez HF, Varea A, Seoane AI. Protein Energy Malnutrition. Does the in vitro Zinc Sulfate Supplementation Improve Chromosomal Damage repair? Biol Trace Elem Res 2014; 162: 64-71.
Riggio O, Ridola L, Pasquale C. Hepatic encephalopathy therapy: An overview. World J Gastrointest Pharmacol Ther 2010; 1: 54-63.
Schliess F, Gorg B, Haussinger D. RNA oxidation and zinc in hepatic encephalopathy and hyperammonemia. Metab Brain Dis 2009; 24: 119-34.
Shawcross DL, Shabbir SS, Taylor NJ, Hughes RD. Ammonia and the neutrophil in the pathogenesis of hepatic encephalopathy in cirrhosis. Hepatology 2010; 51: 1062-9.
Rabbani P, Prasad AS. Plasma ammonia and liver ornithine transcarbamoylase activity in zinc-deficient rats. Am J Physiol 1978; 235: E203-E206.
Riggio O, Merli M, Capocaccia L, Caschera M, Zullo A, Pinto G, Gaudio E, et al. Zinc supplementation reduces blood ammonia and increases liver ornithine transcarbamylase activity in experimental cirrhosis. Hepatology 1992; 16: 785-9.
Prasad AS. Clinical disorders of zinc deficiency. In: Prasad AS (ed.). Current Topics in Nutrition and Disease. 7th ed. New York: Alan R Liss; 1982, p. 89-119.
YoshidaY, Higashi T, Nouso K, Nakatsukasa H, Nakamura SL, Watanabe A. Feefects of zinc deficiency/zinc supplementation on ammonia metabolism in patients with decompensated liver cirrhosis. Acta Med Okayama 2001; 55: 349-55.
Marchesini G, Fabbri A, Bianchi G, Brizi M, Zoli M. Zinc supplementation and amino acid-nitrogen metabolism in patients with advanced cirrhosis. Hepatology 1996; 23: 1084-92.
Reding P, Duchateau J, Bataille C. Oral zinc supplementation improves hepatic encephalopathy. Results of a randomised controlled trial. Lancet 1984; 2: 493-95.
Van der Rijt CC, Schalm SW, Schat H, Foeken K, De Jong G. Overt hepatic encephalopathy precipitated by zinc deficiency. Gastroenterology 1991; 100: 1114-8.
Riggio O, Ariosto F, Merli M, Caschera M, Zullo A, Balducci G, Ziparo V, et al. Short-term oral zinc supplementation does not improve chronic hepatic encephalopathy. Results of a double-blind crossover trial. Dig Dis Sci 1991; 36: 1204-8.
Kugelmas M. Preliminary observation: Oral zinc sulfate replacement is effective in treating muscle cramps in cirrhotic patients. J Am Coll Nutr 2000; 19: 13-5.
Katayama K, Saito M, Kawaguchi T, Endo R, Sawara K, Nishiguchi S, Kato A, et al. Effect of zinc on liver cirrhosis with hyperammonemia: A preliminary randomized, placebo controlled double-blind trial. Nutrition 2014; 30: 1409-14.
El-Serag HB. Hepatocellular carcinoma. N Engl J Med 2011; 365: 1118-27.
Toyokuni S. Role of iron in carcinogenesis: cancer as a ferrotoxic disease. Cancer Sci 2009; 100: 9-16.
Georgakilas AG, Mosley WG, Georgakila S, Ziech D, Panayiotidis MI. Viral-induced human carcinogenesis: an oxidative stress perspective. Mol Biosyst 2010; 6: 1162-72.
El Serag HB, Kanwal F. Epidemiology of Hepatocellular Carcinoma in the United States. Where are we? Where do we go? Hepatology 2014; 60: 1767-75.
Ebara M, Fukuda H, Hatano R, Saisho H, Nagato Y, Suzuki K, Nakajima K, et al. Relationship between copper, zinc and metallothionein in hepatocellular carcinoma and its surrounding liver parenchyma. J Hepatol 2000; 33: 415-22.
Galloway P, McMillan DC, Sattar N. Effect of the inflammatory response on trace element and vitamin status. Ann Clin Biochem 2000; 37: 289-97.
Grüngreiff K, Hebell T, Gutensohn K, Reinhold A, Reinhold D. Plasma concentrations of zinc, copper, interleukin-6 and interferon-gamma, and plasma dipeptidyl peptidase IV activity in chronic hepatitis C. Mol Med Report 2009; 2: 63-8.
Jie J, Hao S, Hongxiu Y, Huiying Y, Jun M, Chenji W, Mingjie Y, et al. Evaluation of Cu in hepatocellular carcinoma by particle induced X-ray emission. J Trace Elem Med Biol 2007; 21: 255-60.
Overbeck S, Rink L, Haase H. Modulating the immune response by oral zinc supplementation: a single approach for multiple diseases. Arch Immunol Ther Exp 2008; 56: 15-30.
Taylor K, Gee J, Kille P. Zinc and cancer. In: Rink L. (ed.) Zinc in Human Health. 1st ed. Amsterdam: IOS Press 2011, p. 283-304.
Zhang Y, Chen C, Yao Q, Li M. ZIP4 upregulates the expression of neuropilin-1, vascular endothelial growth factor, and matrix metalloproteases in pancreatic cancer cell lines and xenografts. Cancer Biol Ther 2010; 9: 236-42.
Hogstrand C, Kille P, Nicholson RI, Taylor KM. Zinc transporters and cancer: a potential role for ZIP7 as a hub for tyrosine kinase activation. Trends Mol Med 2009; 15: 101-11.
Schouwink G. De hepato-cerebrale degeneratie. Thesis, University of Amsterdam, 1961.
Hoogenard TU. Paradigm shift in treatment of Wilson‚s disease: zinc therapy now treatment of choice. Brain Dev 2006; 8: 141-6.
Huster D. Wilson disease. Best Pract Res Clin Gastroenterol 2010; 24: 531-9.
Iorio R, Ranucci G. Wilson disease: A Matter of Copper, But Also of Zinc. J Pediatr Gastroenterol Nutr 2015; 60: 423-4.
Marcellini M, Ciommo VD, Callea F, Devito R, Comparacola D, Sarorelli MR. Treatment of Wilson’s disease with zinc from the time of diagnosis in pediatrics patients: A single hospital 10-year follow up study. J Lab Clin Med 2005; 145: 139-43.
Ranucci G, Socha P, Iorio R. Wilson disease: what is unclear in pediatric patients? Clin Res Hepatol Gastroenterol 2014; 38: 268-72.
Castillo-Higuerto L, Romero-Gomez M, Suarez E, Castro M. Acute hepatitis after starting zinc therapy in a patient with presymptomatic Wilson’s disease. Hepatology 2000; 32: 877.
Roberts EA. Zinc toxicity: from “no, never” to “hardly fever”. Gastroenterology 2011; 140: 1132-5.
Prasad AS. Discovery of human zinc deficiency: impact on human health and disease. Adv Nutr 2013; 4: 176-90.