Alcoholism pp 45-56 | Cite as

Free Radical Mediated Reactions and Ethanol Toxicity: Some Considerations on the Methodological Approaches

  • Emanuelle Albano
  • Magnus Ingelman-Sundberg
  • A. Tomasi
  • G. Poli
Part of the NATO ASI Series book series (NSSA, volume 206)


In the last few years the occurrence of free radical-mediated reactions, including lipid peroxidation, as a result of ethanol intoxication have received new attention, and it is now generally accepted that oxidative damages might play a role in the pathogenesis of tissue damage due to alcohol abuse (Lieber, 1988). Nonetheless, it should be realized that since the early work of Di Luzio, who first suggested an involvement of lipid peroxidation in causing liver lesions following ethanol poisoning (Di Luzio and Hartman, 1967; Comporti et al., 1967), this topic has been a matter of a long standing debate. The main reason of such a controversy is the fact that the results obtained in different laboratories have often been contradictory because of methodological differences (Videla and Valenzuela, 1982; Dianzani, 1985), and also because of the use of analytical techniques not always suitable for the detection of low levels of radical-associated tissue damage.


Lipid Peroxidation Electron Spin Resonance Electron Spin Resonance Spectroscopy Chronic Ethanol Spin Trapping 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Albano, E., Tomasi, A., Goria-Gatti, L. and Dianzani, M.U., 1986, Free radical metabolism of ethanol, in: “Free Radicals Cell Damage and Disease,” C. Rice-Evans, ed., pp. 117–126, Richelieu Press, London.Google Scholar
  2. Albano, E., Cheeseman, K.H., Carini, R., Dianzani, M.U. and Slater, T.F., 1986, Effects of spin traps in isolated hepatocytes and liver microsomes, Biochem. Pharmacol. 35: 257.CrossRefGoogle Scholar
  3. Albano, E., Tomasi, A., Goria-Gatti, L., Poli, G., Vannini, V. and Dianzani, M.U., 1987, Free radical metabolism of alcohols by rat liver microsomes, Free Rad.Res. Communs. 3: 234.Google Scholar
  4. Albano, E., Tomasi, A., Goria-Gatti, L. and Dianzani, M.U., 1988a, Spin trapping of free radical species produced during the microsomal metabolism of ethanol, Chem. Biol. Interact. 65: 223.PubMedCrossRefGoogle Scholar
  5. Albano, E., Poli, G., Tomasi, A., Goria-Gatti, L. and Dianzani, M.U., 1988b, Study on the mechanisms responsible for ethanol-induced oxidative damage using isolated hepatocytes, in: Medical, Biochemical and Chemical Aspects of Free Radicals, Hayaishi, O., Niki, E., Kondo, M. and Yoshikawa, T. eds., pp. 1389–1392, Elsevier, Amsterdam.Google Scholar
  6. Albano, E., Tomasi, A., Goria-Gatti, L., Persson, J.O., Terelius, Y., Goria-Gatti, L., Dianzani, M.U. and Ingelman-Sundberg, M., Role of ethanol-inducible cytochrome P-450 (P-450IIE1) in catalyzing the free radical activation of aliphatic alcohols, Biochem.Pharmacol.,in press.Google Scholar
  7. Burk, R.F. and Ludden, T.M., 1989, Exhalated alkanes as indices of in vivo lipid peroxidation, Biochem. Pharmacol. 38: 1029.PubMedCrossRefGoogle Scholar
  8. Carini, R., Mazzanti, R., Biasi, F., Chiarpotto, E., Marmo, G., Moscarella, S., Gentilini, P., Dianzani, M.U. and Poli, G., 1988, Fluorescence aldehyde protein adducts in the blood serum of healthy alcoholics, in: Alcohol Toxicity and Free Radical Mechanisms, Nordmann, R., Ribière, C. and Rouach, H. eds., pp. 61–64, Pergamon Press, Oxford.Google Scholar
  9. Cederbaum, A.I. and Dikers, E., 1983, Inhibition of microsomal oxidation of alcohol and hydroxyl radical scavengers by the iron chelating agent desferrioxamine, Biochem J. 210: 107.PubMedGoogle Scholar
  10. Cederbaum, A.I., Dikers, E. and Cohen, G., 1978, Effect of hydroxyl radical scavengers on microsomal oxidation of alcohols and associated microsomal reactions, Biochem. 17: 3558.Google Scholar
  11. Comporti, M., Hartman, A.D. and Di Luzio, N.R., 1967, Effect of lipid peroxidation, Lab.Invest. 16: 616.PubMedGoogle Scholar
  12. Corongiu, F.P., Banni, S. and Dessì, M.A., 1989, Conjugated dienes detected in tissue lipid extracts by second derivative spectrophotometry, Free Rad.Biol.Med. 7: 183PubMedCrossRefGoogle Scholar
  13. Di Luzio, N.R. and Hartman, A.D., 1967, Role of lipid peroxidation in the pathogenesis of ethanol induced fatty liver, Fed.Proc. 26: 1463.Google Scholar
  14. Dianzani, M.U., 1985, Lipid peroxidation in ethanol poisoning: a critical reconsideration, Alcohol Alcoholism 20: 161.Google Scholar
  15. Dormandy, T.L., 1988, Diene conjugation in chronic alcoholics, in: Alcohol Toxicity and Free Radical Mechanisms, Nordmann, R., Ribière, C. and Rouach, H., eds., pp. 5559, Pergamon Press, Oxford.Google Scholar
  16. Ekström, G. and Ingelman-Sundberg, M., 1989, Rat liver microsomal NADPH-supported oxidase activity and lipid peroxidation dependent on ethanol-inducible cytochrome P450 (P-450IIE1), Biochem.Pharmacol. 38: 1313.PubMedCrossRefGoogle Scholar
  17. Esterbauer, H. and Cheeseman, K.H., 1990, Determination of aldehydic lipid peroxidation products with special attention to malonaldehyde and 4-hydroxynonenal, Methods Enzymol., 186: 407.PubMedCrossRefGoogle Scholar
  18. Gutteridge, J.M.C. and Halliwell, B., 1990, The measurement and the mechanism of lipid peroxidation in biological systems, Trends Biochem. Sci., 15: 129PubMedCrossRefGoogle Scholar
  19. Hashimoto, S. and Recknagel, R.O., 1968, No chemical evidence of lipid peroxidation in acute ethanol toxicity, Exp. Mol. Pathol, 8: 225.PubMedCrossRefGoogle Scholar
  20. Inomata, T., Ananda Rao, G. and Tsukamoto, H., 1987, Lack of evidence for increased lipid peroxidation in ethanol-induced centrilobular necrosis of rat liver, Liver, 7: 233.PubMedGoogle Scholar
  21. Janzen, E., 1980, A critical review of spin trapping in biological systems, in: “Free Radicals in Biology”, vol. 4 pp.116–150, W.A. Pryor, ed., Academic Press, New York.Google Scholar
  22. Kato, S., Kavase, T., Alderman, J., Inatomi, N. and Lieber, C.S., 1990, Role of xanthine oxidase in ethanol-induced lipid peroxidation in rats, Gastroenterol. 98: 203Google Scholar
  23. Kavase, T., Kato, S. and Lieber, C.S., 1989, Lipid peroxidation and antioxidant defense systems in rat liver after chronic ethanol feeding, Hepatol. 10: 815.CrossRefGoogle Scholar
  24. Keller, F., Snider, A.B., Petracek, T.J. and Sancier, K.M., 1971, Hepatic free radical levels in ethanol-treated and carbon tetrachloride-treated rats, Biochem. Pharmacol. 20: 2507.PubMedCrossRefGoogle Scholar
  25. Kera, Y., Komura, S., Ohbora, Y., Kiriyama, T. and Inoue, K., 1985, Ethanol induced changes in lipid peroxidation and non protein sulphydryl content: different effects in rat liver and kidney, Res.Comm.Chem.Pathol.Pharmacol. 47: 203.Google Scholar
  26. Knecht, K.T., Bradfort, B:U:, Mason, R.P. and Thurman, G.R., 1990, Detection of a- hydroxyethyl free radical from ethanol in vivo, Mol.Pharmacol., 38:26Google Scholar
  27. Lieber, C.S., 1988, Biochemical and molecular basis of alcohol-induced injury to liver and other tissues, New Engl.J. Med., 319: 463.Google Scholar
  28. Litov, R.E., Inving, O.H., Downey, J.F. and Tappel, A.L., 1978, Lipid peroxidation: a mechanism involved in acute ethanol toxicity as demonstrated by in vivo pentane production in the rat, Lipids, 13: 305.PubMedCrossRefGoogle Scholar
  29. MacDonald, C.M., 1973, The effect of ethanol on hepatic lipid peroxidation and on the activity of glutathione reductase and peroxidase, FEBS Lett, 35: 227PubMedCrossRefGoogle Scholar
  30. Miyazawa, T., 1989, Determination of phospholipid hydro-peroxides in human blood by chemioluminescence-HPLC assay, Free Rad.Biol.Med., 7:209PubMedCrossRefGoogle Scholar
  31. Moscarella, S., Laffi, G., Coletta, D., Arena, U., Cappellini, A.P. and Gentilini, P., 1984, Volatile hydrocarbons in the breath of patients with chronic alcoholic liver disease: a possible marker of ethanol induced lipo-peroxidation. in: Frontiers of Gastrointestinal Research, vol. 8, P. Gentilini and M.U. Dianzani, eds., pp. 208–216, Krager, Basel.Google Scholar
  32. Mowri, H., Ohkuma, S. and Takano, T., 1988, Monoclonal DLRIa/ 104G antibodies recognized peroxidized lipoproteins in atherosclerotic lesions, Biochim.Biophys.Acta, 963: 208.PubMedGoogle Scholar
  33. Muller, A. and Sies, H., 1982, Role of ethanol dehydrogenase activity and of acetaldehyde in ethanol-induced ethane and pentane production by isolated perfused rat liver, Biochem.J., 206: 153.PubMedGoogle Scholar
  34. Niki, E., 1987, Antioxidants in relation to lipid peroxidation, Chem.Phys Lipids, 44: 227.PubMedCrossRefGoogle Scholar
  35. Nordmann, R., Ribière, C. and Rouach, H., 1990, Ethanol-induced lipid peroxidation and oxidative stress in extrahepatic tissues, Alcohol Alcoholism, 23: 213.Google Scholar
  36. Peters, T.J., O’Connell, M.J., Venkatesan, S. and Ward, R.J., 1986 Evidence for free radical-mediated damage in experimental and human alcoholic liver disease, in: “Free Radicals Cell Damage and Disease,” pp. 99–110, Rice-Evans, C. ed., Richelieu Press, London.Google Scholar
  37. Reinke, L.A., Lai, E.K., Du Bose, C.M. and McCay, P.B., 1987, Reactive free radical generation in vivo in heart and liver of ethanol-fed rats: correlation with radical formation in vitro, Proc.Natl.Acad.Sci. 84: 8223.CrossRefGoogle Scholar
  38. Reitz, R.C., 1975, A possible mechanism for the peroxidation of lipids due to chronic ethanol ingestion, Biochim. Biophys. Acta, 380:1Google Scholar
  39. Rouach, H., Houzè, P., Orfanelli, M.T., Gentil, M., Bourdon, R. and Nordmann, R., 1990, Effect of acute ethanol administration on the subcellular distribution of iron in rat liver and cerebellum, Biochem. Pharmacol. 39: 1095.PubMedCrossRefGoogle Scholar
  40. Shaw, S., Jayatilleke, E. and Lieber, C.S., 1989, Lipid peroxidation as a mechanism of alcoholic liver injury: Role of iron mobilization and microsomal induction. Alcohol, 5: 135.CrossRefGoogle Scholar
  41. Shaw, S., Jayatilleke, E., Ross, W.A., Gordon, E.R. and Lieber, C.S., 1981, Ethanol induced lipid peroxidation: potentiation by long term alcohol feeding and attenuation by methionine, J.Lab.Clin.Med. 98: 417.PubMedGoogle Scholar
  42. Shaw, S., Rubin, K.P., Lieber, C.S., 1983, Depressed hepatic glutathione and increased diene conjugates in alcoholic liver disease. Evidence of lipid peroxidation, Dig.Dis. Sci. 28: 585.PubMedCrossRefGoogle Scholar
  43. Sippel, H.W., 1983, Effect of an acute dose of ethanol on lipid peroxidation and on the activity of glutathione S-transferase in rat liver, Acta Pharmacol.Toxicol., 53: 135.CrossRefGoogle Scholar
  44. Speisky, H., Bunout, D., Orrego, H., Giles, H.G., Gunasecara, A. and Israel, Y., 1985, Lack of changes in diene conjugate levels following ethanol induced glutathione depletion or hepatic necrosis, Res.Commun.Chem.Pathol. 48: 77.Google Scholar
  45. Suematzu, T., Matsumura, T., Sato, N., Miyamoto, T., Ooka, T., Kamada, T. and Abe, H., 1981, Lipid peroxidation in alcoholic liver disease in humans, Alcohol.Clin.Exp. Res. 5: 427.CrossRefGoogle Scholar
  46. Tanaka, A., Ikegarni, F., Okumura, Y., Hasumura, Y., Kanayama, R. and Takeuki, J., 1970, Effect of alcohol in liver of rats-III. The role of lipid peroxidation and sulphydryl compounds in ethanol-induced liver injury, Lab.Invest. 23: 421.Google Scholar
  47. Tanner, A.R., Bantock, I., Hinks, L., Lloyd, B., Turner, N.R. and Wright, R., 1986, Depressed selenium and vitamin E levels in alcoholic population. Possible relationship to hepatic injury through increased lipid peroxidation, Dig. Dis. Sci. 31: 1307.PubMedCrossRefGoogle Scholar
  48. Thompson, S. and Smith, M.T., 1985, Measurement of diene conjugated from linoleic acid in plasma by high performance liquid chromatography: a questionable non-invasive assay for free radical activity?, Chem.-Biol. Interact. 55: 357.PubMedCrossRefGoogle Scholar
  49. Torrielli, V., Gabriel, L. and Dianzani, M.U., 1978, Ethanol-induced hepatotoxicity: experimental observations on the role of lipid peroxidation, J. Pathol. 126: 11.PubMedCrossRefGoogle Scholar
  50. Umeki, S., Shiojiri, H. and Nozawa, Y., 1984, Chronic ethanol administration decreases fatty acyl-CoA desaturase activities in rat liver microsomes, FEBS Lett. 169: 274.PubMedCrossRefGoogle Scholar
  51. Valenzuela, A., Fernandez, N., Ugarte, G. and Videla, L.A., 1980, Effect of acute ethanol ingestion on lipid peroxidation and on the activity of the enzymes related to peroxide metabolism in the rat, FEBS Lett. 111: 11.PubMedCrossRefGoogle Scholar
  52. Videla, L.A. and Valenzuela, A., 1982, Alcohol ingestion, liver glutathione and lipid peroxidation: metabolic inter-relations and pathological implications, Life Sci. 31: 2395.PubMedCrossRefGoogle Scholar
  53. Videla, L.A. Fernandez, V., Ugarte, G., Valenzuela, A. and Villanueva, A., 1980, Effect of acute ethanol intoxication on the content of reduced glutathione of the liver in relation to its lipoperoxidative capacity in the rats, FEBS Lett. 111: 6.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Emanuelle Albano
    • 1
    • 2
    • 3
  • Magnus Ingelman-Sundberg
    • 1
    • 2
    • 3
  • A. Tomasi
    • 1
    • 2
    • 3
  • G. Poli
    • 1
    • 2
    • 3
  1. 1.Dept. of Experimental Medicine and OncologyUniversity of TurinTurinItaly
  2. 2.Dept. of Physiological ChemistryKarolinska InstitutetStockholmSweden
  3. 3.Institute of General PathologyUniversity of ModenaModenaItaly

Personalised recommendations