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Decreased glutathione in patients with anorexia nervosa. Risk factor for toxic liver injury?

Abstract

Objective: To investigate glutathione and amino acids related to glutathione metabolism in patients with anorexia nervosa in order to test the hypothesis that these patients exhibit a deficiency of glutathione and therefore might be at an increased risk of developing toxic liver injury.

Design: Controlled observatory study and case report.

Setting: University Hospital.

Subjects: Subjects included 11 female patients with anorexia nervosa and 12 healthy female controls.

Interventions: Determination of fasting free and total glutathione, homocysteine, vitamins B6 and B12 and folic acid in plasma.

Results: A 14-y-old patient with a body mass index of 12.6 kg/m2 presented with markedly elevated transaminases (ALAT >50 × upper limit of normal), and paracetamol was detected in her blood. Patients with anorexia nervosa exhibited lower circulating concentrations of free cysteine (8.9±1.5 vs 12.0±1.4 μmol/l) and free and total glutathione (5.0±1.3 vs 7.1±1.2 and 11.2±3.8 vs 16.2±5.0 μmol/l, respectively). The plasma concentrations of homocysteine (17.5±4.9 vs 12.0±3.8 μmol/l) and also of glycine (194±37 vs 143±41 μmol/l) and glutamine (422±51 vs 353±51 μmol/l) were significantly higher in patients with anorexia nervosa who were not deficient in folic acid, vitamin B6 and B12.

Conclusions: Lower plasma concentrations of glutathione suggest lower intracellular concentrations of the tripeptide. Higher homocysteine, glycine and glutamine concentrations point to a decreased utilization of these amino acids for glutathione synthesis and an impairment of trans-sulfuration. Consequently, the capacity of patients with anorexia nervosa to detoxify electrophilic metabolites and reactive oxygen species via glutathione may be impaired.

Sponsorship: Supported by Grant 32-52608.97 from the Swiss National Foundation for Scientific Research.

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References

  • Adams Jr JD, Lauterburg BH & Mitchell JR (1983): Plasma glutathione and glutathione disulfide in the rat: regulation and response to oxidative stress. J. Pharmacol. Exp. Ther. 227, 749–754.

    CAS  PubMed  Google Scholar 

  • Barbaro G, Di Lorenzo G, Soldini M, Parrotto S, Bellomo G, Belloni G, Grisorio B & Barbarini G (1996): Hepatic glutathione deficiency in chronic hepatitis C: quantitative evaluation in patients who are HIV positive and HIV negative and correlations with plasmatic and lymphocytic concentrations and with the activity of the liver disease. Am. J. Gastroenterol. 91, 2569–2573.

    CAS  PubMed  Google Scholar 

  • Bernhard MC, Junker E, Hettinger A & Lauterburg BH (1998): Time course of total cysteine, glutathione and homocysteine in plasma of patients with chronic hepatitis C treated with interferon-alpha with and without supplementation with N-acetylcysteine. J. Hepatol. 28, 751–755.

    Article  CAS  Google Scholar 

  • Bidlingmeyer BA, Cohen SA & Tarvin TL (1984): Rapid analysis of amino acids using pre-column derivatization. J. Chromatogr. 336, 93–104.

    Article  CAS  Google Scholar 

  • Bui MH (1999): A microbiological assay on microtitre plates of thiamine in biological fluids and foods. Int. J. Vitam. Nutr. Res. 69, 362–366.

    Article  CAS  Google Scholar 

  • Cooper AJ (1983): Biochemistry of sulfur-containing amino acids. Annu. Rev. Biochem. 52, 187–222.

    Article  CAS  Google Scholar 

  • Croner S, Larsson J, Schildt B & Symreng T (1985): Severe anorexia nervosa treated with total parenteral nutrition. Clinical course and influence on clinical chemical analyses. Acta Paediatr. Scand. 74, 230–236.

    Article  CAS  Google Scholar 

  • Fukusako T, Negoro K, Tsuda N, Kato M & Morimatsu M (1995): A case of secondary carnitine deficiency due to anorexia nervosa and severe liver damage. Rinsho Shinkeigaku 35, 34–37.

    CAS  PubMed  Google Scholar 

  • Furuta S, Ozawa Y, Maejima K, Tashiro H, Kitahora T, Hasegawa K, Kuroda S & Ikuta N (1999): Anorexia nervosa with severe liver dysfunction and subsequent critical complications. Intern. Med. 38, 575–579.

    Article  CAS  Google Scholar 

  • Griffith OW & Meister A (1979): Glutathione: interorgan translocation, turnover, and metabolism. Proc. Natl. Acad. Sci. USA 76, 5606–5610.

    Article  CAS  Google Scholar 

  • Hammond CL, Lee TK & Ballatori N (2001): Novel roles for glutathione in gene expression, cell death, and membrane transport of organic solutes. J Hepatol. 34, 946–954.

    Article  CAS  Google Scholar 

  • Higashi T, Tateishi N, Naruse A & Sakamoto Y (1977): A novel physiological role of liver glutathione as a reservoir of L-cysteine. J. Biochem. (Tokyo) 82, 117–124.

    Article  CAS  Google Scholar 

  • Hutteroth TH, Wagner R & Knolle J (1977): Schwere toxische Leberschaedigung nach Ueberdosierung von parenteral verabreichten Kohlenhydraten. Med. Klin. 72, 703–707.

    CAS  PubMed  Google Scholar 

  • Jewell SA, Di Monte D, Gentile A, Guglielmi A, Altomare E & Albano O (1986): Decreased hepatic glutathione in chronic alcoholic patients. J. Hepatol. 3, 1–6.

    Article  CAS  Google Scholar 

  • Komuta M, Harada M, Ueno T, Uchimura Y, Inada C, Mitsuyama K, Sakisaka S, Sata M & Tanikawa K (1998): Unusual accumulation of glycogen in liver parenchymal cells in a patient with anorexia nervosa. Intern. Med. 37, 678–682.

    Article  CAS  Google Scholar 

  • Lauterburg BH & Velez ME (1988): Glutathione deficiency in alcoholics: risk factor for paracetamol hepatotoxicity. Gut 29, 1153–1157.

    Article  CAS  Google Scholar 

  • Lu SC (1999): Regulation of hepatic glutathione synthesis: current concepts and controversies. FASEB J. 13, 1169–1183.

    Article  CAS  Google Scholar 

  • McClain CJ, Kromhout JP, Peterson FJ & Holtzman JL (1980): Potentiation of acetaminophen hepatotoxicity by alcohol. JAMA 244, 251–253.

    Article  CAS  Google Scholar 

  • Mehta S, Nain CK, Yadav D, Sharma B & Mathur VS (1985): Disposition of acetaminophen in children with protein calorie malnutrition. Int. J. Clin. Pharmacol. Ther. Toxicol. 23, 311–315.

    CAS  PubMed  Google Scholar 

  • Moyano D, Vilaseca MA, Artuch R & Lambruschini N (1998a): Plasma amino acids in anorexia nervosa. Eur. J. Clin. Nutr. 52, 684–689.

    Article  CAS  Google Scholar 

  • Moyano D, Vilaseca MA, Artuch R, Valls C & Lambruschini N (1998b): Plasma total-homocysteine in anorexia nervosa. Eur. J. Clin. Nutr. 52, 172–175.

    Article  CAS  Google Scholar 

  • Moyano D, Sierra C, Brandi N, Artuch R, Mira A, Garcia-Tornel S & Vilaseca MA (1999): Antioxidant status in anorexia nervosa. Int. J. Eat Disord. 25, 99–103.

    Article  CAS  Google Scholar 

  • Newton GL, Dorian R & Fahey RC (1981): Analysis of biological thiols: derivatization with monobromobimane and separation by reverse-phase high-performance liquid chromatography. Anal. Biochem. 114, 383–387.

    Article  CAS  Google Scholar 

  • Nordgren L & von Scheele C (1977): Hepatic and pancreatic dysfunction in anorexia nervosa: a report of two cases. Biol. Psychiatry 12, 681–686.

    CAS  PubMed  Google Scholar 

  • Nurk E, Tell GS, Nygard O, Refsum H, Ueland PM & Vollset SE (2001): Plasma total homocysteine is influenced by prandial status in humans: the Hordaland homocysteine study. J. Nutr. 131, 1214–1216.

    Article  CAS  Google Scholar 

  • Pessayre D, Dolder A, Artigou JY, Wandscheer JC, Descatoire V, Degott C & Benhamou JP (1979): Effect of fasting on metabolite-mediated hepatotoxicity in the rat. Gastroenterology 77, 264–271.

    CAS  PubMed  Google Scholar 

  • Rahman I & MacNee W (2000): Oxidative stress and regulation of glutathione in lung inflammation. Eur. Respir. J. 16, 534–554.

    Article  CAS  Google Scholar 

  • Reed DJ & Orrenius S (1977): The role of methionine in glutathione biosynthesis by isolated hepatocytes. Biochem. Biophys. Res. Commun. 77, 1257–1264.

    Article  CAS  Google Scholar 

  • Reid M, Badaloo A, Forrester T, Morlese JF, Frazer M, Heird WC & Jahoor F (2000): In vivo rates of erythrocyte glutathione synthesis in children with severe protein-energy malnutrition. Am. J. Physiol. Endocrinol. Metab. 278, E405–E412.

    Article  CAS  Google Scholar 

  • Rivera-Nieves J, Kozaiwa K, Parrish CR, Iezzoni J & Berg CL (2000): Marked transaminase elevation in anorexia nervosa. Dig. Dis. Sci. 45, 1959–1963.

    Article  CAS  Google Scholar 

  • Schenker S, Speeg Jr KV, Perez A & Finch J (2001): The effects of food restriction in man on hepatic metabolism of acetaminophen. Clin. Nutr. 20, 145–150.

    Article  CAS  Google Scholar 

  • Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E & Benjamin SB (1986): Acetaminophen hepatotoxicity in alcoholics. A therapeutic misadventure. Ann. Intern. Med. 104, 399–404.

    Article  CAS  Google Scholar 

  • Staal FJ, Ela SW, Roederer M, Anderson MT & Herzenberg LA (1992): Glutathione deficiency and human immunodeficiency virus infection. Lancet 339, 909–912.

    Article  CAS  Google Scholar 

  • Tateishi N, Higashi T, Shinya S, Naruse A & Sakamoto Y (1974): Studies on the regulation of glutathione level in rat liver. J. Biochem. (Tokyo) 75, 93–103.

    Article  CAS  Google Scholar 

  • Whitcomb DC & Block GD (1994): Association of acetaminophen hepatotoxicity with fasting and ethanol use. JAMA 272, 1845–1850.

    Article  CAS  Google Scholar 

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Correspondence to B H Lauterburg.

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Zenger, F., Russmann, S., Junker, E. et al. Decreased glutathione in patients with anorexia nervosa. Risk factor for toxic liver injury?. Eur J Clin Nutr 58, 238–243 (2004). https://doi.org/10.1038/sj.ejcn.1601772

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