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Role of manganese in hepatic encephalopathy

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Encephalopathy and Nitrogen Metabolism in Liver Failure

Abstract

Hepatic encephalopathy (HE) refers to a spectrum of neuropsychiatric disturbances that can progress to coma. The most common form of HE is acute HE or portal-systemic encephalopathy complicating cirrhosis. A widely accepted view is that HE is caused by an accumulation of ammonia, and most apparently effective forms of therapy for HE are based on the concept that ammonia is neurotoxic1,2 However, not all data are consistent with this theory. In addition to ammonia, levels of manganese become elevated in the brain in HE.3,4 Neurological changes strikingly similar to HE are found in manganese neurotoxicity (manganism), a brain disorder characterized by extrapyramidal dysfunction, that resembles Parkinson’s disease.5 Similar findings in the brains of patients with manganese neurotoxicity and those with HE suggest that this metal may play a role in the pathophysiology of HE.6,7 However, the pathogenetic events in HE are complex, and the role of manganese in liverdisease is not fully understood. Nevertheless, toxic effects of both manganese and ammonia appear to involve an inhibition of mitochondrial function and impaired energy metabolism, which affects astrocytes in particular.8,9 In this review we examine the role of manganese in the pathogenesis of HE by comparing the effects of both ammonia and manganese on astrocyte integrity.

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References

  1. Butterworth RF, Giguere JF, Michaud J, Lavoie J and Layrargues GP. Ammonia: key factor in the pathogenesis of hepatic encephalopathy. Neurochem Pathol 1987; 6: 1–12.

    Article  PubMed  CAS  Google Scholar 

  2. Blei AT. Diagnosis and treatment of hepatic encephalopathy. Baillieres Best Pract Res Clin Gastroenterol 2000; 14: 959–974.

    Article  PubMed  CAS  Google Scholar 

  3. Spahr L, Butterworth RF, Fontaine S, Bui L, Themen G, Milette PC, Lebrun LH, Zayed J, Leblanc A and Pomier-Layrargues G. Increased blood manganese in cirrhotic patients: relationship to pallidal magnetic resonance signal hyperintensity and neurological symptoms. Hepatology 1996; 24: 1116–1120.

    Article  PubMed  CAS  Google Scholar 

  4. Rose C, Butterworth RF, Zayed J, Normandin L, Todd K, Michalak A, Spahr L, Huet PM and Pomier-Layrargues G. Manganese deposition in basal ganglia structures results from both portal-systemic shunting and liver dysfunction. Gastroenterology 1999; 117: 640–644.

    Article  PubMed  CAS  Google Scholar 

  5. Yamada M, Ohno S, Okayasu I, Okeda R, Hatakeyama S, Watanabe H, Ushio K and Tsukagoshi H. Chronic manganese poisoning: a neuropathological study with determination of manganese distribution in the brain. Acta Neuropathol (Berl) 1986; 70: 273–278.

    Article  CAS  Google Scholar 

  6. Weissenborn K, Ehrenheim C, Hori A, Kubicka S and Manns MP. Pallidal lesions in patients with liver cirrhosis: clinical and MRI evaluation. Metab Brain Dis 1995; 10:219–231.

    Article  PubMed  CAS  Google Scholar 

  7. Pomier Layrargues G, Rose C, Spahr L, Zayed J, Normandin L and Butterworth RF. Role of manganese in the pathogenesis of PSE. Metab Brain Dis 1998; 13, 311–317.

    Article  Google Scholar 

  8. Norenberg MD. The role of astrocytes in hepatic encephalopathy. Neurochem Pathol 1987; 6: 13–33.

    Article  PubMed  CAS  Google Scholar 

  9. Tiffany-Castiglion E and Qian Y. Astroglia as metal depots: molecular mechanisms for metal accumulation, storage and release. Neurotoxicology 2001; 22: 577–592.

    Article  PubMed  CAS  Google Scholar 

  10. Hindfeld B, Plum F and Duffy TE. Effect of acute ammonia intoxication on cerebral metabolism in rats with portacaval shunts. J Clin Invest 1977; 59: 386–396.

    Article  Google Scholar 

  11. Kramer L, Tribl B, Gendo A, Zauner C, Schneider B, Ferenci P, and Madl C. Partial pressure of ammonia versus ammonia in hepatic encephalopathy. Hepatology 2000; 31: 30–34.

    Article  PubMed  CAS  Google Scholar 

  12. Cooper AJ and Plum F. Biochemistry and physiology of brain ammonia. Physiol Rev 1987; 67: 440–519.

    PubMed  CAS  Google Scholar 

  13. Chamuleau RA and Vogels BA. Hyperammonaemia without portal systemic shunting does not resemble hepatic encephalopathy. Adv Exp Med Biol 1997; 420: 173–183.

    Article  PubMed  CAS  Google Scholar 

  14. Papavasiliou PS, Miller ST and Cotzias GC. Role of liver in regulating distribution and excretion of manganese. Am J Physiol 1966; 211: 211–216.

    PubMed  CAS  Google Scholar 

  15. Pomier-Layrargues G, Spahr L and Butterworth RF. Increased manganese concentrations in pallidum of cirrhotic patients. Lancet 1995; 345: 735.

    Article  PubMed  CAS  Google Scholar 

  16. Krieger D, Krieger S, Jansen O, Gass P, Theilmann L and Lichtnecker H. Manganese and chronic hepatic encephalopathy. Lancet 1995; 346: 270–274.

    Article  PubMed  CAS  Google Scholar 

  17. Newland MC, Ceckler TL, Kordower JH and Weiss B. Visualizing manganese in the primate basal ganglia with magnetic resonance imaging. Exp Neurol 1989; 106: 251–258.

    Article  PubMed  CAS  Google Scholar 

  18. Nelson K, Golnick J, Korn T and Angle C. Manganese encephalopathy: utility of early magnetic resonance imaging. Br J Ind Med 1993; 50: 510–513.

    PubMed  CAS  Google Scholar 

  19. Kim Y, Kim KS, Yang JS, Park IJ, Kim E, Jin Y, Kwon KR, Chang KH, Kim JW, Park SH, Lim HS, Cheong HK, Shin YC, Park J and Moon Y. Increase in signal intensities on T1-weighted MRI in asymptomatic manganese-exposed workers. Neurotoxicology 1999; 20: 901–907.

    PubMed  CAS  Google Scholar 

  20. Pal PK, Samii A and Calne DB. Manganese neurotoxicity: a review of clinical features, imaging and pathology. Neurotoxicology 1999; 20: 227–238.

    PubMed  CAS  Google Scholar 

  21. Versieck J, Barbier F, Speecke A and Hoste J. Normal manganese concentrations in human serum. Acta Endocrinol (Copenh) 1974; 76: 783–788.

    CAS  Google Scholar 

  22. Hauser RA, Zesiewicz TA, Rosemurgy AS, Martinez C and Olanow CW. Manganese intoxication and chronic liver failure. Ann Neurol 1994; 36: 871–875.

    Article  PubMed  CAS  Google Scholar 

  23. Lazeyras F, Spahr L, DuPasquier R, Delavelle J, Burkhard P, Hadengue A, Hochstrasser D, Mentha G, Giostra E, Terrier F and Vingerhoets F. Persistence of mild parkinsonism 4 months after liver transplantation in patients with preoperative minimal hepatic encephalopathy: a study on neuroradiological and blood manganese changes. Transpl Int 2002; 15: 188–195.

    Article  PubMed  Google Scholar 

  24. Taylor-Robinson SD, Oatridge A, Hajnal JV, Burroughs AK, McIntyre N and deSouza NM. MR imaging of the basal ganglia in chronic liver disease: correlation of T1-weighted and magnetisation transfer contrast measurements with liver dysfunction and neuropsychiatric status. Metab Brain Dis 1995; 10: 175–188.

    Article  PubMed  CAS  Google Scholar 

  25. Inoue E, Hori S, Narumi Y, Fujita M, Kuriyama K, Kadota T and Kuroda C. Portal-systemic encephalopathy: presence of basal ganglia lesions with high signal intensity on MR images. Radiology 1991;179:551–555.

    PubMed  CAS  Google Scholar 

  26. Ejima A, Imamura T, Nakamura S, Saito H, Matsumoto and Momono S. Manganese intoxication during total parenteral nutrition. Lancet 1992; 339: 426.

    Article  PubMed  CAS  Google Scholar 

  27. Pujol A, Pujol J, Graus F, Rimola A, Peri J, Mercader JM, Garcia-Pagan JC, Bosch J, Rodes J and Tolosa E. Hyperintense globus pallidus on T1-weighted MRI in cirrhotic patients is associated with severity of liver failure. Neurology 1993; 43: 65–69.

    Article  PubMed  CAS  Google Scholar 

  28. Subhash MN and Padmashree TS. Regional distribution of dopamine beta-hydroxylase and monoamine oxidase in brains of rats exposed to manganese. Food Chem Toxicol 1990; 28: 567–570.

    Article  PubMed  CAS  Google Scholar 

  29. Bergeron M, Reader TA, Layrargues GP and Butterworth RF. Monoamines and metabolites in autopsied brain tissue from cirrhotic patients with HE. Neurochem Res 1989; 14: 853–859.

    Article  PubMed  CAS  Google Scholar 

  30. Mousseau DD, Perney P, Layrargues GP and Butterworth RF. Selective loss of pallidal dopamine D2 receptor density in hepatic encephalopathy. Neurosci Lett 1993; 162: 192–196.

    Article  PubMed  CAS  Google Scholar 

  31. Mergler D and Baldwin M. Early manifestations of manganese neurotoxicity in humans: an update. Environ Res 1997; 73: 92–100.

    Article  PubMed  CAS  Google Scholar 

  32. Norenberg MD. Astrocytic-ammonia interactions in hepatic encephalopathy. Semin Liver Dis 1996; 16: 245–253.

    Article  PubMed  CAS  Google Scholar 

  33. Aschner M, Vrana KE and Zheng W. Manganese uptake and distribution in the central nervous system (CNS). Neurotoxicology 1999; 20: 173–180.

    PubMed  CAS  Google Scholar 

  34. Spranger M, Schwab S, Desiderato S, Bonmann E, Krieger D and Fandrey J. Manganese augments nitric oxide synthesis in murine astrocytes: a new pathogenetic mechanism in manganism? Exp Neurol 1998; 149: 277–283.

    Article  PubMed  CAS  Google Scholar 

  35. Henriksson J and Tjalve H. Manganese taken up into the CNS via the olfactory pathway in rats affects astrocytes. Toxicol Sci 2000; 55: 392–398.

    Article  PubMed  CAS  Google Scholar 

  36. Sobel RA, DeArmond SJ, Forno LS and Eng LF. Glial fibrillary acidic protein in hepatic encephalopathy. An immunohistochemical study. J Neuropathol Exp Neurol 1981; 40: 625–632.

    Article  PubMed  CAS  Google Scholar 

  37. Pentschew A, Ebner FF, and Kovatch RM. Experimental manganese encephalopathy in monkeys: a preliminary report. J Neuropathol Exp Neurol 1963; 22: 488–499.

    Article  PubMed  CAS  Google Scholar 

  38. Olanow CW, Good PF, Shinotoh H, Hewitt KA, Vingerhoets F, Snow BJ, Beal MF, Calne DB and Perl DP. Manganese intoxication in the rhesus monkey: a clinical, imaging, pathologic, and biochemical study. Neurology 1996; 46: 492–498.

    Article  PubMed  CAS  Google Scholar 

  39. Norenberg MD, Neary JT, Norenberg LO and McCarthy M. Ammonia induced decrease in glial fibrillary acidic protein in cultured astrocytes. J Neuropathol Exp Neurol 1990; 49: 399–405.

    Article  PubMed  CAS  Google Scholar 

  40. Eriksson H, Tedroff J, Thuomas KA, Aquilonius SM, Hartvig P, Fasth KJ, Bjurling P, Langstrom B, Hedstrom KG and Heilbronn E. Manganese induced brain lesions in Macaca fascicularis as revealed by PET and magnetic resonance imaging. Arch Toxicol 1992; 66: 403–407.

    Article  PubMed  CAS  Google Scholar 

  41. Wiltfang J, Nolte W, Otto M, Wildberg J, Bahn E, Figulla HR, Pralle L, Hartmann H, Ruther E and Ramadori G. Elevated serum levels of astroglial S100beta in patients with liver cirrhosis indicate early and subclinical portal-systemic encephalopathy. Metab Brain Dis 1999; 14: 239–251.

    Article  PubMed  CAS  Google Scholar 

  42. Zheng W, Zhao Q, Slavkovich V, Aschner M and Graziano JH. Alteration of iron homeostasis following chronic exposure to manganese in rats. Brain Res 1999; 833: 125–132.

    Article  PubMed  CAS  Google Scholar 

  43. Chen CJ and Liao SL. Oxidative stress involved in astrocytic alterations induced by manganese. Exp Neurol 2002; 175: 216–225.

    Article  PubMed  CAS  Google Scholar 

  44. Lo MM and Snyder SH. Two distinct solubilized benzodiazepine receptors: differential modulation by ions. J Neurosci 1983; 3: 2270–2279.

    PubMed  CAS  Google Scholar 

  45. Ha JH and Basile AS. Modulation of ligand binding to components of the GABAA receptor complex by ammonia: implications for the pathogenesis of hyperammonemic syndromes. Brain Res 1996; 720: 35–44.

    Article  PubMed  CAS  Google Scholar 

  46. Jones EA and Basile AS. Does ammonia contribute to increased GABA-ergic neurotransmission in liver failure? Metab Brain Dis 1998; 13: 351–360.

    Article  PubMed  CAS  Google Scholar 

  47. Butterworth RF. The astrocytic (“peripheral-type”) benzodiazepine receptor: role in the pathogenesis of portal-systemic encephalopathy. Neurochem Int 2000; 36: 411–416.

    Article  PubMed  CAS  Google Scholar 

  48. Butterworth RF, Lavoie J, Giguere JF and Pomier-Layrargues G. Affinities and densities of high-affinity [3H]muscimol (GAB A-A) binding sites and of central benzodiazepine receptors are unchanged in autopsied brain tissue from cirrhotic patients with with hepatic encephalopathy. Hepatology 1988; 8: 1084–1088.

    Article  PubMed  CAS  Google Scholar 

  49. Itzhak Y and Norenberg MD. Ammonia-induced upregulation of peripheral-type benzodiazepine receptors in cultured astrocytes labeled with [3H]PK 11195. Neurosci Lett 1994; 177: 35–38.

    Article  PubMed  CAS  Google Scholar 

  50. Hazell AS, Desjardins P and Butterworth RF. Chronic exposure of rat primary astrocyte cultures to manganese results in increased binding sites for the ‘peripheral-type’ benzodiazepine receptor ligand 3H-PK 11195. Neurosci Lett 1999; 271: 5–8.

    Article  PubMed  CAS  Google Scholar 

  51. Giguere JF, Hamel E and Butterworth RF. Increased densities of binding sites for the’ peripheral-type’ benzodiazepine receptor ligand [3H]PK 11195 in rat brain following portacaval anastomosis. Brain Res 1992;585:295–298.

    Article  PubMed  CAS  Google Scholar 

  52. Lavoie J, Layrargues GP and Butterworth RF. Increased densities of peripheral-type benzodiazepine receptors in brain autopsy samples from cirrhotic patients with HE. Hepatology 1990; 11: 874–878.

    Article  PubMed  CAS  Google Scholar 

  53. Paul SM and Purdy RH. Neuroactive steroids. FASEB J 1992; 6: 2311–2322.

    PubMed  CAS  Google Scholar 

  54. Garcia-Segura LM, Chowen JA, Parducz A and Naftolin F. Gonadal hormones as promoters of structural synaptic plasticity: cellular mechanisms. Prog Neurobiol 1994; 44: 279–307.

    Article  PubMed  CAS  Google Scholar 

  55. Norenberg MD, Itzhak Y and Bender AS. The peripheral benzodiazepine receptor and neurosteroids in hepatic encephalopathy. Adv Exp Med Biol 1997; 420: 95–111.

    Article  PubMed  CAS  Google Scholar 

  56. Anholt RR, Pedersen PL, De Souza EB and Snyder SH. The peripheral-type benzodiazepine receptor. Localization to the mitochondrial outer membrane. J Biol Chem 1986; 261: 576–583.

    PubMed  CAS  Google Scholar 

  57. Berson A, Descatoire V, Sutton A, Fau D, Maulny B, Vadrot N, Feldmann G, Berthon B, Tordjmann T and Pessayre D. Toxicity of alpidem, a peripheral benzodiazepine receptor ligand, but not Zolpidem, in rat hepatocytes: role of mitochondrial permeability transition and metabolic activation. J Pharmacol Exp Ther 2001; 299: 793–800.

    PubMed  CAS  Google Scholar 

  58. Bai G, Rama Rao KV, Murthy CR, Panickar KS, Jayakumar AR and Norenberg MD. Ammonia induces the mitochondrial permeability transition in primary cultures of rat astrocytes. J Neurosci Res 2001;66:981–991.

    Article  PubMed  CAS  Google Scholar 

  59. Gavin CE, Gunter KK and Gunter TE. Manganese and calcium transport in mitochondria: implications for manganese toxicity. Neurotoxicology 1999; 20: 445–453.

    PubMed  CAS  Google Scholar 

  60. Schliess F, Gorg B, Fischer R, Desjardins P, Bidmon HJ, Herrmann A, Butterworth RF, Zilles K and Haussinger D. Ammonia induces MK-801-sensitive nitration and phosphorylation of protein tyrosine residues in rat astrocytes. FASEB J 2002; 16:739–741.

    PubMed  CAS  Google Scholar 

  61. Hazell AS and Norenberg MD. Ammonia and manganese increase arginine uptake in cultured astrocytes. Neurochem Res 1998; 23: 869–873.

    Article  PubMed  CAS  Google Scholar 

  62. Kosenko E, Kaminsky Y, Lopata O, Muravyov N, Kaminsky A, Hermenegildo C and Felipo V. Nitroarginine, an inhibitor of nitric oxide synthase, prevents changes in superoxide radical and antioxidant enzymes induced by ammonia intoxication. Metab Brain Dis 1998; 13: 29–41.

    Article  PubMed  CAS  Google Scholar 

  63. Desole MS, Esposito G, Migheli R, Fresu L, Sircana S, Zangani D, Miele M and Miele E. Cellular defence mechanisms in the striatum of young and aged rats subchronically exposed to manganese. Neuropharmacology 1995; 34: 289–295.

    Article  PubMed  CAS  Google Scholar 

  64. Rao VL, Audet RM and Butterworth RF. Increased nitric oxide synthase activities and L-[3H]arginine uptake in brain following portacaval anastomosis. J Neurochem 1995; 65: 677–678.

    PubMed  CAS  Google Scholar 

  65. Butterworth RF. In: Arias IM, Boyer JL, Chisari FV, Fausto N, Schachter, D and Shafritz DA (Eds). The liver: Biology and Pathobiology. Philadelphia: Lippincott Williams & Wilkins, 2001: 633–647.

    Google Scholar 

  66. Brouillet EP, Shinobu L, McGarvey U, Hochberg F and Beal MF. Manganese injection into the rat striatum produces excitotoxic lesions by impairing energy metabolism. Exp Neurol 1993; 120: 89–94.

    Article  PubMed  CAS  Google Scholar 

  67. Cano G, Suarez-Roca H and Bonilla E. Manganese poisoning reduces strychnine-insensitive glycine binding sites in the globus pallidus of the mouse brain. Invest Clin 1996; 37: 209–219.

    PubMed  CAS  Google Scholar 

  68. Taylor-Robinson SD, Sargentoni J, Mallalieu RJ, Bell JD, Bryant DJ, Coutts GA and Morgan MY. Cerebral phosphorus-31 magnetic resonance spectroscopy in patients with chronic hepatic encephalopathy. Hepatology 1994; 20: 1173–1178.

    Article  PubMed  CAS  Google Scholar 

  69. Gavin CE, Gunter KK and Gunter TE. Mn +2 sequestration by mitochondria and inhibition of oxidative phosphorylation. Toxicol Appl Pharmacol 1992; 115:1–5.

    Article  PubMed  CAS  Google Scholar 

  70. Morgan MY. Noninvasive neuroinvestigation in liver disease. Semin Liver Dis 1996; 16: 293–314.

    Article  PubMed  CAS  Google Scholar 

  71. Taylor-Robinson SD, Sargentoni J, Oatridge A, Bryant DJ, Hajnal JV, Marcus CD, Seery JP, Hodgson HJ and deSouza NM. MR imaging and spectroscopy of the basal ganglia in chronic liver disease: correlation of T1-weighted contrast measurements with abnormalities in proton and phosphorus-31 MR spectra. Metab Brain Dis 1996; 11: 249–268.

    Article  PubMed  CAS  Google Scholar 

  72. Astore D and Boicelli CA. Hyperammonemia and chronic hepatic encephalopathy: an in vivo PMRS study of the rat brain. MAGMA 2000; 10: 160–166.

    PubMed  CAS  Google Scholar 

  73. Patel N, Forton DM, Coutts GA, Thomas HC and Taylor-Robinson SD. Intracellular pH measurements of the whole head and the basal ganglia in chronic liver disease: a phosphorus-31 MR spectroscopy study. Metab Brain Dis 2000; 15: 223–240.

    PubMed  CAS  Google Scholar 

  74. Zwingmann C, Brand A, Richter-Landsberg C and Leibfritz D. Multinuclear NMR spectroscopy studies on NH4Cl-induced metabolic alterations and detoxification processes in primary astrocytes and glioma cells. Dev Neurosci 1998; 20: 417–426.

    Article  PubMed  CAS  Google Scholar 

  75. Hazell AS, Desjardins P and Butterworth RF. Increased expression of glyceraldehyde-3-phosphate dehydrogenase in cultured astrocytes following exposure to manganese. Neurochem Int 1999; 35: 11–17.

    Article  PubMed  CAS  Google Scholar 

  76. Zheng W, Ren S and Graziano JH. Manganese inhibits mitochondrial aconitase: a mechanism of manganese neurotoxicity. Brain Res 1998; 799: 334–342.

    Article  PubMed  CAS  Google Scholar 

  77. Hietanen E, Kilpio J and Savolainen H. Neurochemical and biotransformational enzyme responses to manganese exposure in rats. Arch Environ Contam Toxicol 198; 10: 339–345.

    Google Scholar 

  78. Lai JC and Cooper AJ. Brain alpha-ketoglutarate dehydrogenase complex: kinetic properties, regional distribution, and effects of inhibitors. J Neurochem 1986; 47: 1376–1386.

    Article  PubMed  CAS  Google Scholar 

  79. Lockwood AH, Yap EW, Rhoades HM and Wong WH. Altered cerebral blood flow and glucose metabolism in patients with liver disease and minimal encephalopathy. J Cereb Blood Flow Metab 1991; 11:331–336.

    Article  PubMed  CAS  Google Scholar 

  80. Trzepacz PT, Tarter RE, Shah A, Tringali R, Faett DG and Van Thiel DH. SPECT scan and cognitive findings in subclinical hepatic encephalopathy. J Neuropsychiatry Clin Neurosci 1994; 6: 170–175.

    PubMed  CAS  Google Scholar 

  81. Lill DW, Mountz JM and Darji JT. Technetium-99m-HMPAO brain SPECT evaluation of neurotoxicity due to manganese toxicity. J Nucl Med 1994; 35:863–866.

    PubMed  CAS  Google Scholar 

  82. Themen G, Giguere JF and Butterworth RF. Increased cerebrospinal fluid lactate reflects deterioration of neurological status in experimental portal-systemic encephalopathy. Metab Brain Dis 1991;6:225–231.

    Article  Google Scholar 

  83. Lowry, OH, and Passonneau JV. Kinetic evidence for multiple binding sites on phsophofructokinase. J Biol Chem 1966; 241: 2268–2279.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Medicine, Hôpital Saint-Luc (CHUM), Montreal, Quebec, Canada

    C. Zwingmann & A. S. Hazell

  2. Department of Organic Chemistry, University of Bremen, Bremen, Germany

    D. Leibfritz

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  1. C. Zwingmann
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Editors and Affiliations

  1. Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, Netherlands

    E. Anthony Jones  & Robert A. F. M. Chamuleau  & 

  2. Department of Biochemistry, Academic Medical Center, Amsterdam, Netherlands

    Alfred J. Meijer

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Zwingmann, C., Leibfritz, D., Hazell, A.S. (2003). Role of manganese in hepatic encephalopathy. In: Jones, E.A., Meijer, A.J., Chamuleau, R.A.F.M. (eds) Encephalopathy and Nitrogen Metabolism in Liver Failure. Springer, Dordrecht. https://doi.org/10.1007/978-94-010-0159-5_27

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