Pathophysiological Relevance of Free Radicals to the Ethanol-Induced Disorders in Membrane Lipids

  • Roger Nordmann
  • Catherine Ribière
  • Hélène Rouach
Part of the NATO ASI Series book series (NSSA, volume 189)


Numerous studies have shown that ethanol administration is followed by changes in the membranous lipids, especially at the level of the phospholipid polyunsaturated fatty acid side chains. These changes in the membrane lipid composition have been suggested to modify membrane fluidity and thereby play a role in prominent manifestations of alcohol abuse such as tolerance to or dependence on ethanol (1). They have also been implied as important causative factors in many aspects of ethanol toxicity.


Lipid Peroxidation Chronic Ethanol Ethanol Oxidation Ethanol Administration Acute Ethanol 
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  1. 1.
    D. B. Goldstein, Ethanol-induced adaptation in biological membranes, Ann. N.Y. Acad. Sci. 492: 103–111 (1987).PubMedCrossRefGoogle Scholar
  2. 2.
    N. R. Di Luzio, Prevention of the acute ethanol-induced fatty liver by the simultaneous administration of anti-oxidants, Life Sci. 3: 113–118 (1964).CrossRefGoogle Scholar
  3. 3.
    N. R. Di Luzio and A. D. Hartman, Role of lipid peroxidation in the pathogenesis of ethanol-induced fatty liver, Federation Proc. 26: 1436–1442 (1967).Google Scholar
  4. 4.
    M. U. Dianzani, Lipid peroxidation in ethanol poisoning: a critical reconsideration, Alcohol Alcoholism 20: 161–173 (1985).Google Scholar
  5. 5.
    L. A. Reinke, E. K. Lai, C. M. Du Bose and P. B. Mc Cay, Reactive free radical generation in vivo in heart and liver of ethanol-fed rats: Correlation with radical formation in vitro, Proc. Natl. Acad. Sci. USA, 84: 9 223–9 227 (1987).Google Scholar
  6. 6.
    B. Halliwell and J. M. C. Gutteridge, Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts, Arch. Biochem. Biophys. 246: 501–5 4 (1986).Google Scholar
  7. 7.
    H. Sies, Oxidative stress: Introductory remarks, in: “Oxidative Stress”, H. Sies, ed., Acad. Press, London, pp. 1–8 (1985).Google Scholar
  8. 8.
    A. I. Cederbaum, Microsomal generation of hydroxyl radicals: its role in microsomal ethanol oxidizing system (MEOS) activity and requirement for iron, Ann. N.Y. Acad. Sci. 492: 35–49 (1987).PubMedCrossRefGoogle Scholar
  9. 9.
    G. Ekström and M. Ingelman-Sundberg, Mechanisms of lipid peroxidation dependent upon cytochrome P-450 LM(2), Eur. J. Biochem. 158: 195–201 (1986).PubMedCrossRefGoogle Scholar
  10. 10.
    M. Ingelman-Sundberg, G. EkstrÖm and N. Tindberg, Lipid peroxidation dependent on ethanol-inducible cytochrome P-450 from rat liver, in: “Advances in the Biosciences, vol. 71: Alcohol Toxicity and Free Radical Mechanisms”, R. Nordmann, C. Ribière and H. Rouach, eds., Pergamon Press, Oxford, pp. 43–48 (1988).Google Scholar
  11. 11.
    G. Ekström, T. Cronholm and M. Ingelman-Sundberg, Hydroxyl-radical production and ethanol oxidation by liver microsomes isolated from ethanol-treated rats, Biochem. J. 233: 755–761 (1986).PubMedGoogle Scholar
  12. 12.
    S. Shaw, E. Jayatilleke and C. S. Lieber, The effect of chronic alcohol feeding on lipid peroxidation in microsomes: Lack of relationship to hydroxyl radical generation, Biochem. Biophys. Res. Comm. 118: 233–238 (1984).Google Scholar
  13. 13.
    G. Minotti and S. D. Aust, The requirement for iron (III) in the initiation of lipid peroxidation by iron (II) and hydrogen peroxide, J. Biol. Chem. 262: 1098–1104 (1987).PubMedGoogle Scholar
  14. 14.
    T. F. Slater, Hepatotoxic effects of alcohol, in: “Free Radical Mechanisms in Tissue Injury”, Pion Ltd., London, pp. 171–197 (1972).Google Scholar
  15. 15.
    E. Albano, A. Tomasi, L. Goria-Gatti, G. Poli, V. Vannini and M. U. Dianzani, Free radical metabolism of alcohols by rat liver microsomes, Free Radical Res. Comm. 3: 243–249 (1987).Google Scholar
  16. 16.
    T. F. Slater, Free radical mechanisms in tissue injury with special reference to the cytotoxic effects of ethanol and related alcohols, in: “Advances in the Biosciences, vol. 71: Alcohol Toxicity and Free Radical Mechanisms”, R. Nordmann, C. Ribière and H. Rouach, eds., Pergamon Press, Oxford, pp. 1–9 (1988).Google Scholar
  17. 17.
    H. Rouach, M. K. Park, M. T. Orfanelli, B. Janvier, P. Brissot, M. Bourel and R. Nordmann, Effects of ethanol on hepatic and cerebellar lipid peroxidation and endogenous antioxidants in naive and chronic iron overloaded rats, in: “Advances in the Biosciences, vol.71: Alcohol Toxicity and Free Radical Mechanisms”, R. Nordmann, C.Ribière and H.Rouach, eds., Pergamon Press, Oxford, pp.49–54(1988).Google Scholar
  18. 18.
    H. Rouach, M. Clément, M. T. Orfanelli, B. Janvier, J. Nordmann and R. Nordmann, Hepatic lipid peroxidation and mitochondrial susceptibility to peroxidative attacks during ethanol inhalation and withdrawal, Biochim. Biophys. Acta 753 • 439–444 (1983).Google Scholar
  19. 19.
    J. Sinaceur, C. Legendre, J. Montagne, M. Jagueux, L. Orcel and R. Nordmann, Prevention by desferrioxamine (DFO) of the-hepatic ultrastructural lesions induced in the rat by chronic ethanol administration, Alcohol Alcoholism 22: A10 (1987).Google Scholar
  20. 20.
    C. Ribière, D. Sabourault, J. Sinaceur, R. Nordmann, C. Houée-Levin, and C. Ferradini, Radiolysis study of the reaction of desferrioxa-mine with 0 free radicals, in: “Superoxide and Superoxide Dismu-tase in Chemistry, Biology and Medicine”, G. Rotilio, ed., Elsevier, Amsterdam, pp. 47–49 (1986).Google Scholar
  21. 21.
    H.J. Forman and A. Boveris, Superoxide radical and hydrogen peroxide in mitochondria, in: “Free Radicals in Biology”, vol.5, W. A. Pryor, ed., Academic Press, New-York, pp. 65–90 (1982).Google Scholar
  22. 22.
    J. Sinaceur, C. Ribière, D. Sabourault and R. Nordmann, Superoxide formation in liver mitochondria during ethanol intoxication: possible role in alcohol hepatotoxicity, in: “Free Radicals in Liver Injury”, G. Poli, K. H. Cheeseman, M. U. Dianzani and T. F. Slater, eds., IRL Press, Oxford, pp. 175–177 (1988).Google Scholar
  23. 23.
    H. H. H. Oei, H. C. Zoganas, J. M. McCord and S. W. Schaffer, Role of acetaldehyde and xanthine oxidase in ethanol-induced oxidative stress, Res. Comm. Chem. Pathol. Pharmacol. 51: 195–203 (1986).Google Scholar
  24. 24.
    L. G. Sultatos, Effects of acute ethanol administration on the hepatic xanthine dehydrogenase-oxidase system in the rat, J. Pharmacol. Exp. Ther. 246: 946–949 (1988).PubMedGoogle Scholar
  25. 25.
    A. Jacobs, Low molecular weight intracellular iron transport compounds, Blood 50: 433–439 (19 77).Google Scholar
  26. 26.
    H. Roùach, P. Houzé, M. T. Orfanelli, M. Gentil, R. Bourdon and R. Nordmann, Effect of acute ethanol administration on the subcellular distribution of iron in rat liver and cerebellum, Submitted for publication.Google Scholar
  27. 27.
    R. Nordmann, C. Ribière and H. Rouach, Involvement of iron and iron-catalyzed free radical production in ethanol metabolism and toxicity, Enzyme 37: 57–69 (1987).PubMedGoogle Scholar
  28. 28.
    M. G. Irving, J. W. Halliday and L. W. Powell, Association between alcoholism and increased hepatic iron stores, Alcoholism Clin. Exp. Res. 12: 7–13 (1988).Google Scholar
  29. 29.
    L. A. Videla, V. Fernandez, A. de Marinis, N. Fernandez and A. Valenzuela, Liver lipoperoxidative pressure and glutathione status following acetaldehyde and aliphatic alcohols pretreatments in rat, Biochem. Biophys. Res. Comm. 104: 965–970 (1982).CrossRefGoogle Scholar
  30. 30.
    A. Müller and H. Sies, Alcohol, aldehydes and lipid peroxidation: current notions, in: “Advances in Biomedical Alcohol Research”, K. O. Lindros, R. Ylikhari and K. Kiianmaa, eds., Pergamon Press, Oxford, pp. 67–74 (1987).Google Scholar
  31. 31.
    H. Antébi, C. Ribière, J. Sinaceur, C. Abu-Murad and R. Nordmann, Involvement of oxygen radicals in ethanol oxidation and in the ethanol-induced decrease in liver glutathione, in: “Oxygen Radicals in Chemistry and Biology”, W. Bors, M. Saran and D. Tait, eds., De Gruyter, Berlin, pp. 757–760 (1984).Google Scholar
  32. 32.
    B. Halliwell, Free radicals and metal ions in health and disease, Proc. Nutrition Soc. 46: 13–26 (1987).Google Scholar
  33. 33.
    P. M. Sinet, R. E. Heikkila and G. Cohen, Hydrogen peroxide production by rat brain in vivo, J. Neurochem. 34. 1421–1428 (1980).PubMedCrossRefGoogle Scholar
  34. 34.
    R. Nordmann, Oxidative stress from alcohol in the brain, in. “Advances in Biomedical Alcohol Research”, K. O. Lindros, R. Ylikhri and K. Kiianmaa, eds., Pergamon Press, Oxford, pp. 75–82 (1987).Google Scholar
  35. 35.
    R. Nordmann, C. Ribière and H. Rouach, Free radicals and oxidative stress: their implication in the metabolism and toxicity of ethanol, in: “Biomedical and Social Aspects of Alcohol and Alcoholism”, K. Kuriyama, A Takada and H. Ishii, eds., Excerpta Medica, Amsterdam, pp. 17–27 (1988).Google Scholar
  36. 36.
    C. Abu-Murad and R. Nordmann, Reduction in severity of physical dependence on ethanol in mice caused by desferrioxamine administration, Pharmacol. Biochem. Behay. 18: 515–517 (1983).CrossRefGoogle Scholar
  37. 37.
    L. F. Panchenko, S. V. Pirozhkov, S. V. Popova and V. D. Antonenkov, Effect of chronic ethanol treatment on peroxisomal acyl-CoA oxidase activity and lipid peroxidation in rat liver and heart, Experientia 43: 580–581 (1987).PubMedCrossRefGoogle Scholar
  38. 38.
    E. Rosemblum, J. S. Gavaler and D. H. Van Thiel, Lipid peroxidation: a mechanism for ethanol-associated testicular injury in rats, Endocrinology 116: 3 11–3 18 (1985).Google Scholar
  39. 39.
    Y. Kera, S. Komura, Y. Ohbora, T. Kiriyama and K. Inone, Ethanol induced changes in lipid peroxidation and non protein sulhydryl content, Res. Comm. Chem. Pathol. Pharmacol. 47: 203–209 (1985).Google Scholar
  40. 40.
    S. Shaw, K. P. Rubin and C. S. Lieber, Depressed hepatic glutathione and increased diene conjugates in alcoholic liver disease. Evidence of lipid peroxidation, Digest. Diseases Sciences 28: 585–589 (1983).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Roger Nordmann
    • 1
  • Catherine Ribière
    • 1
  • Hélène Rouach
    • 1
  1. 1.Department of Biomedical Research on AlcoholismUniversité René DescartesParis Cedex 06France

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