Effects of Ethanol on Glutathione Metabolism

  • Mack C. Mitchell
  • David S. Raiford
  • Ariane Mallat
Part of the Drug and Alcohol Abuse Reviews book series (DAAR, volume 2)

Abstract

Glutathione (GSH), the most abundant nonprotein thiol in cells, plays a pivotal role in protecting cells against damage from reactive drug metabolites, free radicals, peroxides, and other toxic oxygen species. Within the last decade, there has been substantial progress in understanding the metabolism of glutathione, its functions in cellular detoxification processes, and how these processes are altered by both acute and chronic alcohol consumption. Some evidence suggests that alcohol-related changes in glutathione homeostasis and detoxification may contribute directly or indirectly to the pathogenesis of tissue damage from alcohol. This chapter will summarize briefly the salient features of glutathione metabolism and current understanding of how these are altered by alcohol consumption in experimental animals and in humans

Keywords

Selenium Adduct NADPH Glucagon Paracetamol 

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References

  1. 1.
    A. Meister and M. E. Anderson (1983) Glutathione. Ann. Rev. Biochem. 52 711–760.PubMedGoogle Scholar
  2. 2.
    N. Kaplowitz, T. Y. Aw, and M. Ookhtens (1985) The regulation of hepatic glutathione. Ann. Rev. Pharm. Toxicol. 25 715–744.PubMedGoogle Scholar
  3. 3.
    S. Deneke and B. L. Fanburg (1989) Regulation of cellular glutathione. Am. J. Physiol. 257 L163–173.PubMedGoogle Scholar
  4. 4.
    R. Sekura and A. Meister (1977) y-glutamylcysteine synthetase. Further purification, “half of the sites” reactivity subunits and specificity. J. BioL Chem. 252 2599–2605.PubMedGoogle Scholar
  5. 5.
    S. Yanari, J. E. Snoke, and K. Bloch (1953) Energy sources in glutathione synthesis. J. BioL Chem. 201 561–571.PubMedGoogle Scholar
  6. 6.
    R G. Richman and A. Meister (1975) Regulation of y-glutamylcysteine synthetase by nonallosteric feedback inhibition by glutathione. J. BioL Chem. 250, 1422–1426.Google Scholar
  7. 7.
    B. H. Lauterburg, Y. Vaishnav, W. G. Stiliwell, and J. R. Mitchell (1980) The effects of age and glutathione depletion on hepatic glutathione turnover in vivo determined by acetaminophen probe analysis. PharmacoL Exp. Ther. 213 54–58.Google Scholar
  8. 8.
    D. J. Reed and M. W. Fariss (1984) Glutathione depletion and susceptibility. Pharmacol. Rev. 36 25S–35S.PubMedGoogle Scholar
  9. 9.
    B. A. Arrick, W. Grillo, Z. Cohn, and C. Nathan (1985) Hydrogen peroxide from cellular metabolism of cystine. J. Clin. Invest. 76 567–574.PubMedGoogle Scholar
  10. 11.
    S. Bannai (1984) Transport of cystine and cysteine in mammalian cells. Biochim. Biophys. Acta 779 289–306.PubMedGoogle Scholar
  11. 11.
    M. S. Kilberg, H. N. Christensen, and M. E. Handlogten (1979) Biochem. Biophys. Res. Commun. 88 747–751.Google Scholar
  12. 12.
    N. Tateishi, T. Higashi, A. Naruse, K. Hikita, and Y. Sakamoto (1981) Relative contributions of sulfur atoms of dietary cysteine and methionine to rat liver glutathione and proteins. J. Biochem. 901603–1610.PubMedGoogle Scholar
  13. 13.
    D. J. Reed and S. Orrenius (1977) The role of methionine in glutathione biosynthesis by isolated hepatocytes. Biochem. Biophys. Res. Commun. 77,1257–1264.PubMedGoogle Scholar
  14. l4.
    S. S. Tate and A. Meister (1974) Interaction of y-glutamyl transpeptidase with amino acids, dipeptides, and derivatives and analogs of glutathione. J. Biol. Chem. 2497593–7602.PubMedGoogle Scholar
  15. 15.
    M. E. Anderson and A. Meister (1983) Transport and direct utilization of yglutamylcyst(e)ine for glutathione synthesis. Proc. Natl. Acad. Sci. 80 707–711.PubMedGoogle Scholar
  16. 16.
    G. A. Bartoli and H. Sies (1978) Reduced and oxidized glutathione efflux from the liver. FEBS Lett. 86 89–91.PubMedGoogle Scholar
  17. 17.
    B. H. Lauterburg, J. D. Adams, and J. R. Mitchell (1984) Hepatic glutathione homeostasis in the rat: Efflux accounts for glutathione turnover. Hepatology, 4 586–590.PubMedGoogle Scholar
  18. 18.
    M. Ookhtens, K. Hobdy, M. C. Corvasce, T. Y. Aw, and N. Kaplowitz (1985) Sinusoidal efflux of glutathione in the perfused rat liver. Evidence for a carrier-mediated process. J. Clin. Invest. 75 258–265.PubMedGoogle Scholar
  19. 19.
    T. Y. Aw, M. Ookhtens, C. Ren, and N. Kaplowitz (1986) Kinetics of glutathione efflux from isolated rat hepatocytes. Am. J. Physiol. 250 G236–243.PubMedGoogle Scholar
  20. 20.
    M. Inoue, R. Kinne, T. Tran, and I. M. Arias (1984) Glutathione transport across hepatocyte plasma membranes: Analysis using isolated rat liver sinusoidal-membrane vesicles. Eur. J. Biochem. 138, 491–495.PubMedGoogle Scholar
  21. 21.
    T. Y. Aw, M. Ookhtens, J. F. Kuhlenkamp, and N. Kaplowitz (1987) Trans-stimulation and driving forces for GSH transport in sinusoidal membrane vesicles from rat liver. Biochem. Biophys. Res. Commun. 143 377–382.PubMedGoogle Scholar
  22. 22.
    M. Ookhtens, I. Lyon, J. Fernandez-Checa, and N. Kaplowitz (1988) Inhibition of glutathione efflux in the perfused rat liver and isolated hepatocytes by organic anions and bilirubin. J. Clin. Invest. 82 608–616.PubMedGoogle Scholar
  23. 23.
    N. Ballatori, R. Jacob, C. Barrett, and J. L. Boyer (1988) Biliary catabolism of glutathione and differential reabsorption of its amino acid constituents. Am. J. Physiol. 254 Gl-G7.Google Scholar
  24. 24.
    J. D. Adams, B. H. Lauterburg, and J. R. Mitchell (1983) Plasma glutathione and glutathione disulfide in the rat: Regulation and response to oxidative stress. J. Pharmacol. Exp. Ther. 227 749–754.PubMedGoogle Scholar
  25. 25.
    A. Wendel and P. Cikryt (1980) The level and half-life of glutathione in human plasma. FEBS Lett. 120 209–211.PubMedGoogle Scholar
  26. 26.
    K. E. Hill and R. F. Burk (1985) Effect of selenium deficiency on the disposition of plasma glutathione. Arch. Biochem. Biophys. 240166–171.PubMedGoogle Scholar
  27. 27.
    T. Higashi, N. Tateishi, A. Naruse, and Y. Sakamoto (1977) A novel physiological role of liver glutathione as a reservoir of cysteine. J. Biochem. 82, 117–124.PubMedGoogle Scholar
  28. 28.
    H. Sies and P. Graf (1985) Hepatic thiol and glutathione efflux under the influence of vasopressin, phenylephrine and adrenaline. Biochem. J. 226 545–549.PubMedGoogle Scholar
  29. 29.
    P. J. Lowe, K. Miyal, H. Steinbach, and W. G. M. Hardison (1988) Hormonal regulation of hepatocyte tight junctional permeability. Am. J. Physiol. 255 G454–G461.PubMedGoogle Scholar
  30. 30.
    B. H. Lauterburg and J. R. Mitchell (1981) Regulation of hepatic glutathione turnover in rats in vivo and evidence for kinetic homogeneity of the hepatic glutathione pool. J. Clin. Invest. 671415–1424.PubMedGoogle Scholar
  31. 31.
    S. Lu, C. Garcia-Ruiz, J Kuhlenkamp, M. Ookhtens, and N. Kaplowitz (1990) Hormonal regulation of GSH efflux. Clin. Res. 38424A.Google Scholar
  32. 32.
    T. L. Wright, G. Fitz, and T. D. Boyer (1988) Hepatic efflux of glutathione by the perfused rat liver: Role of membrane potential difference. Am. J. Physiol. 255 G547–G555.Google Scholar
  33. 33.
    D. J. Callans, L. S. Wacker, and M. C. Mitchell (1987) Effects of ethanol feeding and withdrawal on plasma glutathione elimination in the rat. Hepatology 7,496–501.PubMedGoogle Scholar
  34. 34.
    O. W. Griffith and A. Meister (1985) Origin and turnover of mitochondrial glutathione. Proc. Natl. Acad. Sci. USA 82 4668–4672.PubMedGoogle Scholar
  35. 35.
    M. J. Meredith and D. J. Reed (1982) Status of the mitochodrial pool of glutathione in the isolated hepatocyte. J. Biol. Chem. 257 3747–3753.PubMedGoogle Scholar
  36. 36.
    D. J. Reed (1990) Glutathione: Toxicological implications. Ann. Rev. Pharmacol. Toxicol. 30 603–631.Google Scholar
  37. 37.
    D. M. Ziegler (1985) Role of reversible oxidation reduction of enzyme thiolsdisulfides in metabolic regulation. Ann. Rev. Biochem. 54 305–329.PubMedGoogle Scholar
  38. 38.
    J. M. Oliver, D. F. Albertini, and R. D. Berlin (1976) Effects of glutathione oxidizing agents on microtubule assembly and microtubule-dependent surface properties of human neutrophils. J. Cell. Biot. 71 921–932.Google Scholar
  39. 39.
    T. D. Boyer (1989) The glutathione S-transferases: An update. Hepatology 9 486–496.PubMedGoogle Scholar
  40. 40.
    E. Boyland and L. F. Chasseud (1969) The role of glutathione and glutathione S-transferases in mercapturic acid biosynthesis. Advan. Enzymol. 32172–219.Google Scholar
  41. 41.
    H. Sies and K. H. Summer (1975) Hydroperoxide-metabolising systems in rat liver. Eur. J. Biochem. 57 503–512.PubMedGoogle Scholar
  42. 42.
    G. Bellomo and S. Orrenius (1985) Altered thiol and calcium homeostasis in oxidative hepatocellular injury. Hepatology 5 876–882.PubMedGoogle Scholar
  43. 43.
    M. Inoue, R. Kinne, T. Tran, and I. Arias (1983) The mechanism of biliary secretion of reduced glutathione. Analysis of transport process in isolated rat-liver canalicular membrane vesicles. Eur. J. Biochem. 134, 467–471. PubMedGoogle Scholar
  44. 44.
    G. Lindwall and T. D. Boyer (1987) Excretion of glutathione conjugates by primary cultured rat hepatocytes. J. Biol. Chem. 262 5151–5158.PubMedGoogle Scholar
  45. 45.
    R. P. Elferink, R. Ottenhoff, W. Liefting, J. deHaan, and P. L. Jansen (1989) Hepatobiliary transport of glutathione and glutathione conjugate in rats with hereditary hyperbilirubinemia. J. Clin. Invest. 84 476–483.PubMedGoogle Scholar
  46. 46.
    P. Talalay, M. J. De Long, and H. J. Prochaska (1987) Molecular mechanisms in protection against carcinogenesis, in Cancer Biology and Therapeutics. J. G. Cory and A. Szentivanyi, eds. Plenum, New York, pp. 197–216.Google Scholar
  47. 47.
    H. J. Prochaska, M. J. De Long, and P. Talalay (1985) On the mechanisms of induction of cancer-protective enzymes: A unifying proposal. Proc. Natl. Acad. Sci. 82 8232–8236.PubMedGoogle Scholar
  48. 48.
    S. Bannai (1989) Induction of cystine and glutamate transport activity in human fibroblasts by diethylmaleate and other electrophilic agents. J. Biol. Chem. 259 2435–2440.Google Scholar
  49. 49.
    S. M. Deneke, D. F. Baxter, S. T. Phelps, and B. L. Fanburg (1989) Increase in endothelial cell glutathione and precursor amino acid uptake by diethyl maleate and hyperoxia. Am. J. Physiol. 257 L265–L271.PubMedGoogle Scholar
  50. 50.
    A. Takada, F. Ikegami, Y. Okumura, Y. Hasumura, R. Kanayama, and J. Takeuchi (1970) Effect of alcohol on the liver of rats. Lab. Invest. 23 421–428.PubMedGoogle Scholar
  51. 51.
    C. M. MacDonald, J. Dow, and M. R. Moore (1977) A possible protective role for sulphydryl compounds in acute alcoholic liver injury. Biochem. Pharmacol. 261529–1531.PubMedGoogle Scholar
  52. 52.
    V Fernández and L. A. Videla (1981) Effect of acute and chronic ethanol ingestion on the content of reduced glutathione of various tissues of the rat. Experientia 37 392–394.PubMedGoogle Scholar
  53. 53.
    C. Guerri and S. Grisolla (1980) Changes in glutathione in acute and chronic alcohol intoxication. Pharmacol. Biochem. Behan, 13 53–61.Google Scholar
  54. 54.
    Y. Kera, S. Komura, Y. Ohbora, T. Kiriyama, and K. Inoue (1985) Ethanol induced changes in lipid peroxidation and nonprotein sulfhydryl content. Res. Comm. Chem. Pathol. Pharmacol. 47 203–209.Google Scholar
  55. 55.
    L. A. Videla, V. Fernández, N. Fernández, and A. Valenzuela (1981) On the mechanism of the glutathione depletion induced in the liver by acute ethanol ingestion. Subst. Alcohol Actions/Misuse 2153–160.Google Scholar
  56. 56.
    N. Koçak-Toker, M. Uysal, G. Aykaç, S. Yalçin, A. Sivas, and H. Oz (1983) Effect of acute ethanol intoxication on the liver lipid peroxide and glutathione levels in the rat. IRCS Med. Sci. 11 915–916.Google Scholar
  57. 57.
    L. A. Videla, V. Fernández, A. Valenzuela, and G. Ugarte (1981) Effect of (+)-cyanidanol-3 on the changes in liver glutathione content and lipoperoxidation induced by acute ethanol administration in the rat. Pharmacology 22 343–348.PubMedGoogle Scholar
  58. 58.
    B. H. Lauterburg, S. Davies, and J. R. Mitchell (1984) Ethanol suppresses hepatic glutathione synthesis in rats in vivo. J. Pharmacol. Exp. Ther. 230 7–11.Google Scholar
  59. 59.
    H. Speisky, A. MacDonald, G. Giles, H. Orrego, and Y. Israel (1985) Increased loss and decreased synthesis of hepatic glutathione after acute ethanol administration. Biochem. J. 225 565–572.PubMedGoogle Scholar
  60. 60.
    H. Speisky, D. Bunout, H. Orrego, H. G. Giles, A. Gunasekara, and Y. Israel (1985) Lack of changes in diene conjugate levels following ethanol induced glutathione depletion or hepatic necrosis. Res. Comm. Chem. Pathol. Pharmacol. 48 77–90.Google Scholar
  61. 61.
    H. Speisky, Y. Kera, K. E. Penttilä, Y. Israel, and K. O. Lindros (1988) Depletion of hepatic glutathione by ethanol occurs independently of ethanol metabolism. Alcohol. Clin. Exp. Res. 12 224–228.PubMedGoogle Scholar
  62. 62.
    J. Gonzalez, M. E. Muñoz, M. I. Martin, P. S. Collado, J. Fermoso, and A. Esteller (1988) Influence of acute ethanol administration on hepatic glutathione metabolism in the rat. Alcohol 5103–106.PubMedGoogle Scholar
  63. 63.
    S. R. Paredes, P. A. Kozicki, H. Fukuda, M. V. Rossetti, and A. M. Del C. Baffle (1987) S-adenosyl-L-methionine: Its effect on aminolevulinate dehydratase and glutathione in acute ethanol intoxication. Alcohol 4 81–85PubMedGoogle Scholar
  64. 64.
    L. A. Videla and A. Valenzuela (1982) Alcohol ingestion, liver glutathione and lipoperoxidation: Metabolic interrelations and pathological implications. Life Sci. 31 2395–2407.PubMedGoogle Scholar
  65. 65.
    M. P. Schubert (1936) Compounds of thiol acids with aldehydes. J. BioL Chem. 114 341–350.Google Scholar
  66. 66.
    M. P. Schubert (1937) Reactions of semimercaptals with amino compounds. J. BioL Chem. 121,539–548.Google Scholar
  67. 67.
    L. Wlodek (1988) The reaction of sulfhydryl groups with carbonyl compounds. Acta Biochimica Polonica, 35 307–316.PubMedGoogle Scholar
  68. 68.
    Y. Kern, T. Kiriyama, and S. Komura (1985) Conjugation of acetaldehyde with cysteinylglycine, the first metabolite in glutathione breakdown by y-glutamyltranspeptidase. Agents and Actions 17 48–52.Google Scholar
  69. 69.
    J. Viña, J. M. Estrela, C. Guerri, and F. J. Romero (1980) Effect of ethanol on glutathione concentration in isolated hepatocytes. Biochem. J. 188 549–552.PubMedGoogle Scholar
  70. 70.
    L. A. Videla, V. Fernández, and A. de Marinis (1982) Liver lipoperoxidative pressure and glutathione status following acetaldehyde and aliphatic alcohols pretreatments in the rat. Biochem. Biophys. Res. Commun. 104 965–970.PubMedGoogle Scholar
  71. 71.
    J.-M. Burgunder, J. Nelles, M. Bilzer, and B. H. Lauterburg (1988) Ethanol decreases plasma sulphydryls in man: Effect of disulfiram. Eur. J. Clin. Invest. 18 420–424.PubMedGoogle Scholar
  72. 72.
    J. C. Fernández-Checa, M. Ookhtens, and N. Kaplowitz (1987) Effect of chronic ethanol feeding on rat hepatocytic glutathione. Compartmentation, efflux, and response to incubation with ethanol. J. Clin. Invest. 80 57–62.PubMedGoogle Scholar
  73. 73.
    R. H. Johnson, G. Eisenhofer, and D. G. Lambie (1986) The effects of acute and chronic ingestion of ethanol on the autonomic nervous system. Drug Alcohol Depend. 18 319–328.PubMedGoogle Scholar
  74. 74.
    C.-P. Siegers, U. Jeb, and M. Younes (1983) Effects of phenobarbital, GSHdepletors, CCI4 and ethanol on the biliary efflux of glutathione in rats. Arch. Int. Pharmacodyn. 266 315–325.PubMedGoogle Scholar
  75. 75.
    G. Vendemiale, E. Jayatilleke, S. Shaw, and C. S. Lieber (1984) Depression of biliary glutathione excretion by chronic ethanol feeding in the rat. Life Sci. 34 1065–1073.PubMedGoogle Scholar
  76. 76.
    J. M. Hassing, A. L. Hupka, S. J. Stohs, and P. C. Yoon (1979) Hepatic glutathione levels in D-penicillamine-fed ethanol-dependent rats. Res. Comm. Chem. Pathol. Pharmacol. 25 389–394.Google Scholar
  77. 77.
    E. Kaplan, E. G. DeMaster, and H. T. Nagasawa (1980) Effect of pargyline on hepatic glutathione levels in rats treated acutely and chronically with ethanol. Res. Comm. Chem. Pathol. Pharmacol. 30,577–580.Google Scholar
  78. 78.
    C. Hétu, L. Yelle, and J.-G. Joly (1982) Influence of ethanol on hepaticglutathione content and on the activity of glutathione S-transferases and epoxide hydrase in the rat. Drug Metab. Dis. 10 246–250.Google Scholar
  79. 79.
    S. Morton and M. C. Mitchell (1985) Effects of chronic ethanol feeding on glutathione turnover in the rat. Biochem. Pharmacol. 34,1559–1563.PubMedGoogle Scholar
  80. 80.
    J. L. Pierson and M. C. Mitchell (1986) Increased hepatic efflux of glutathione after chronic ethanol feeding. Biochem. Pharmacol. 351533–1537.PubMedGoogle Scholar
  81. 81.
    S. Shaw, E. Jayatilleke, W. A. Ross, E. R. Gordon, and C. S. Lieber (1981) Ethanol-induced lipid peroxidation: Potentiation by long-term alcohol feeding and attenuation by methionine. J. Lab. Clin. Med. 98 417–424.PubMedGoogle Scholar
  82. 82.
    G. Aykaç, M. Uysal, A. S. Yalçin, N. Koçak-Toker, A. Sivas, and H. Oz (1985) The effect of chronic ethanol ingestion on hepatic lipid peroxide, glutathione, glutathione peroxidase and glutathione transferase in rats. Toxicology 36 71–76.PubMedGoogle Scholar
  83. 83.
    J. T. Työppönen and K. O. Lindros (1986) Combined vitamin E deficiency and ethanol pretreatment: Liver glutathione and enzyme changes. Int. J. Vit. Nutr. Res. 56 241–245.Google Scholar
  84. 84.
    M. Uysal, M. Keyer-Uysal, N. Koçak-Toker, and G. Aykaç (1986) The effect of chronic ethanol ingestion on brain lipid peroxide and glutathione levels in rats. Drug Alcohol Depend. 18 73–75.PubMedGoogle Scholar
  85. 85.
    J. Harata, M. Nagata, E. Sasaki, I. Ishiguro, Y. Ohta, and Y. Murakami (1983) Effect of prolonged alcohol administration on activities of various enzymes scavenging activated oxygen radicals and lipid peroxide level in the liver of rats. Biochem. Pharmacol. 321795–1798.PubMedGoogle Scholar
  86. 86.
    M. E. Muñoz, M. I. Martin, J. Fermoso, J. Gonzalez, and A. Esteller (1987) Effect of chronic ethanol feeding on glutathione and glutathione-related enzyme activities in rat liver. Drug Alcohol Depend. 20 221–226.PubMedGoogle Scholar
  87. 87.
    T. Kawase, S. Kat, and C. S. Lieber (1989) Lipid peroxidation and antioxidant defense systems in rat liver after chronic ethanol feeding. Hepatology 10 815–821.PubMedGoogle Scholar
  88. 88.
    J. C. Fernandez-Checa, M. Ookhtens, and N. Kaplowitz (1989) Effects of chronic ethanol feeding on rat hepatocytic glutathione. Relationship of cytosolic glutathione to efflux and mitochondrial sequestration. J. Clin. Invest. 83,1247–1252.PubMedGoogle Scholar
  89. 89.
    A. I. Cederbaum and E. Rubin (1976) Protective effect of cysteine on the inhibition of mitochondrial functions by acetaldehyde. Biochem. Pharmacol. 25 963–973.PubMedGoogle Scholar
  90. 90.
    J. D. Finkelstein, J. P. Cello, and W. E. Kyle (1974) Ethanol-induced changes in methionine metabolism in rat liver. Biochem. Biophys. Res. Commun. 61 525–531.PubMedGoogle Scholar
  91. 91.
    S. Shaw and C. S. Lieber (1980) Increased hepatic production of alpha-aminon-butyric acid after chronic alcohol consumption in rats and baboons. Gastroenterology 78108–113.PubMedGoogle Scholar
  92. 92.
    R. M. David and D. E. Nerland (1983) Induction of mouse liver glutathione S-transferase by ethanol. Biochem. Pharmacol. 32 2809–2811.PubMedGoogle Scholar
  93. 93.
    P. S. Bora, C. A. Spilburg, and L. G. Lange (1989) Metabolism of ethanol and carcinogens by glutathione transferases. Proc. Natl. Acad. Sci. USA 86 4470 1173.Google Scholar
  94. 94.
    P. S. Bora, C. A. Spilburg, and L. G. Lange (1989) Identification of a satellite fatty acid ethyl ester synthase from human myocardium as a glutathione S-transferase. J. Clin. Invest. 84,1942–1946.PubMedGoogle Scholar
  95. 95.
    R. Teschke, M. Neuefeind, M. Nishimura, and G. Strohmeyer (1983) Hepatic gamma-glutamyltransferase activity in alcoholic fatty liver: comparison with other liver enzymes in man and rats. Gut 24 625–630.PubMedGoogle Scholar
  96. 96.
    E. Ivanov, D. Adjarov, M. Etarska, T. Stankushev, K. Brumbarov, and M. Kerimova (1980) Elevated liver gamma-glutamyl transferase in chronic alcoholics. Enzyme 25 304–308.PubMedGoogle Scholar
  97. 97.
    G. Gadeholt, J. Aarbakke, E. Dybing, M. Sjöblom, and J. Morland (1980) Hepatic microsomal drug metabolism, glutamyl transferase activity and in vivo antipyrine half-life in rats chronically fed an ethanol diet, a control diet and a chow diet. J. Pharmacol. Exp. Ther. 213196–203.PubMedGoogle Scholar
  98. 98.
    H. Ishii, S. Yasuraoka, Y. Shigeta, S. Takagi, T. Kamiya, F. Okuno, K. Miyamoto, and M. Tsuchiya (1978) Hepatic and intestinal gammaglutamyltranspeptidase activity: Its activation by chronic ethanol administration. Life Sci. 231393–1398.PubMedGoogle Scholar
  99. 99.
    R. Teschke and A. S. Petrides (1982) Hepatic gamma-glutamyltransferase activity: Its increase following chronic alcohol consumption and the role of carbohydrates. Biochem. Pharmacol. 31 3751–3756.PubMedGoogle Scholar
  100. 100.
    S. Yamada, J. S. Wilson, and C. S. Lieber (1985) The effects of ethanol and diet on hepatic and serum y-glutamyltranspeptidase activities in rats. J. Nutr. 115 1285–1290.PubMedGoogle Scholar
  101. 101.
    H. Spiesky, N. Shackel, G. Varghese D. Wade, and Y. Israel (1990) Role of hepatic y-glutamyltransferase in the degradation of circulating glutathione: Studies in the intact guinea pig perfused liver. Hepatology 11 843–849.Google Scholar
  102. 102.
    H. Speisky, A. Gunasekara, G. Varghese, and Y. Israel (1987) Basolateral gamma-glutamyltransferase ectoactivity in rat liver. Effects of chronic alcohol consumption. Alcohol Alcohol. 1(Suppl) 245–249.Google Scholar
  103. 103.
    S Shaw, K. P. Rubin, and C. S. Lieber (1983) Depressed hepatic glutathione and increased diene conjugates in alcoholic liver disease. Evidence of lipid peroxidation. Dig. Dis. Sci. 28 585–589.PubMedGoogle Scholar
  104. 104.
    K. W. Woodhouse, F. M. Williams, E. Mutch, P. Wright, O. F. W. James, and M. D. Rawlins (1983) The effect of alcoholic cirrhosis on the activities of microsomal aldrin epoxidase, 7-ethoxycoumarin-O DE-ethylase and epoxide hydrolase, and on the concentrations of reduced glutathione in human liver. Br. J. Clin. Pharmacol.15, 667–672.PubMedGoogle Scholar
  105. 105.
    L. A. Videla, H. Iturriaga, M. E. Pino, D. Bunout, A. Valenzuela, and G. Ugarte (1984) Content of hepatic reduced glutathione in chronic alcoholic patients: Influence of the length of abstinence and liver necrosis. Clin. Sci. 66 283–290.PubMedGoogle Scholar
  106. 106.
    S. A. Jewell, D. Di Monte, A. Gentile, A. Guglielmi, E. Altomare, and O. Albano (1986) Decreased hepatic glutathione in chronic alcoholic patients. J. Hepatol. 3,1–6.PubMedGoogle Scholar
  107. 107.
    E. Altomare, G. Vendemiale, and O. Albano (1988) Hepatic glutathione content in patients with alcoholic and non alcoholic liver diseases. Life Sci. 43 991–998.PubMedGoogle Scholar
  108. 108.
    M. C. Mitchell and H. F. Herlong (1986) Alcohol and nutrition: Caloric value, bioenergetics, and relationship to liver damage. Ann. Rev. Nutt: 6,457–474.Google Scholar
  109. 109.
    R. K. Chawla, E W. Lewis, M. H. Kutner, D. M. Bate, R. G. B. Roy, and D. Rudman (1984) Plasma cysteine, cystine, and glutathione in cirrhosis. Gastroenterology, 87 770–776.PubMedGoogle Scholar
  110. 110.
    A. M. Diehl, M. C. Mitchell, H. E Herlong, J. J. Potter, L. Wacker, and E. Mezey (1986) Changes in plasma amino acids during sobriety in alcoholic patients with and without liver disease. Am. J. Clin. Nutr. 44 453–460.PubMedGoogle Scholar
  111. 111.
    S. Shaw, and C. S. Lieber (1978) Plasma amino acid abnormalities in the alcoholic. Respective role of alcohol, nutrition, and liver injury. Gastroenterology, 74 677–682.PubMedGoogle Scholar
  112. 112.
    A. M. Duce, P. Ortiz, C. Cabrero, and J. M. Mato (1988) S-adenosyl-Lmethionine synthetase and phospholipid methyltransferase are inhibited in human cirrhosis. Hepatology 8 65–68.PubMedGoogle Scholar
  113. 113.
    G. Vendemiale, E. Altomare, T. Trizio, C. LeGrazie, C. DiPadova, M. T. Salerno, V. Carrieri, and O. Albano (1989) Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease. Scand. J. Gastroenterol. 24, 407–415.PubMedGoogle Scholar
  114. 114.
    C. S. Lieber, A. Casini, L. M. DeCarli, C. I. Kim, N. Lowe, R. Sasaki, and M. A. Leo (1990) S-adenosyl-L-methionine attenuates alcohol-induced liver injury in the baboon. Hepatology, 11165–172.PubMedGoogle Scholar
  115. 115.
    C. J. McClain, J. P. Kromhout, F. J. Peterson, and J. L. Holtzman (1980) Potentiation of acetaminophen hepatotoxicity by alcohol. JAMA, 244 251–253.PubMedGoogle Scholar
  116. 116.
    L. B. Seeff, B. A. Cuccherini, H. J. Zimmerman, E. Adler, and S. B. Benjamin (1986) Acetaminophen hepatotoxicity in alcoholics. Ann. Int. Med. 104 399–404.PubMedGoogle Scholar
  117. 117.
    B. H. Lauterburg and M. E. Velez (1988) Glutathione deficiency in alcoholics: Risk factor for paracetamol hepatotoxicity. Gut, 291153–1157.PubMedGoogle Scholar
  118. 118.
    A. C. Smith, F. W. Freeman, and R. D. Harbison (1981) Ethanol enhancement of cocaine-induced hepatotoxicity. Biochem. Pharmacol. 30 453–458.PubMedGoogle Scholar
  119. 119.
    C. Sato, Y. Matsuda, and C. S. Lieber (1981) Increased hepatotoxicity of acetaminophen after chronic ethanol consumption in the rat. Gastroenterology, 80 140–148.PubMedGoogle Scholar
  120. 120.
    E. Altomare, M. A. Leo, C. Sato, G. Vendemiale, and C. S. Lieber (1984) Interaction of ethanol with acetaminophen metabolism in the baboon. Biochem. Pharmacol. 33,2207–2212.PubMedGoogle Scholar
  121. 121.
    N. Zampaglione, D. J. Jollow, J. R. Mitchell, B. Stripp, M. Hamrick, and J. R. Gillette (1973) Role of detoxifying enzymes in bromobenzene-induced liver necrosis. J. Pharmacol. Exp. They. 187 218–227.Google Scholar
  122. 122.
    M. Younes and O. Strubelt (1977) Enhancement of hypoxic liver damage by ethanol. Biochem. Pharmacol. 36 2973–2977.Google Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Mack C. Mitchell
  • David S. Raiford
  • Ariane Mallat

There are no affiliations available

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