Hepatotoxicity of Acetaldehyde

  • C. S. Lieber
  • E. Baraona
  • Y. Matsuda
  • M. Salaspuro
  • Y. Hasumura
  • S. Matsuzaki
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 126)


All known pathways of ethanol oxidation in the liver result in production of acetaldehyde. Until recently, however, the fate of this metabolite of ethanol has been rather neglected because of methodological difficulties in its measurement. However, recent technological advancements have permitted the development of acceptable methods to detect acetaldehyde in biological fluids. A number of studies have been initiated which already have documented profound involvement of acetaldehyde in the metabolic and toxic effects of ethanol. This is not an unexpected development, in view of the known chemical reactivity of this metabolite. In this paper, we shall particularly focus on some alterations after chronic ethanol consumption particularly in the liver.


Aldehyde Dehydrogenase Chronic Ethanol Ethanol Oxidation Acetaldehyde Concentration Ethanol Administration 
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  1. Baraona, E., Pirola, R. C. and Lieber, C. S.: The pathogenesis of postprandial hyperlipemia in rats fed ethanol-containing diets. J. Clin. Invest. 52:296, 1973.PubMedCentralPubMedCrossRefGoogle Scholar
  2. Baraona, E., Leo, M., Borowsky, S.A. and Lieber, C. S.: Alcoholic Hepatomegaly: Accimiulation of protein in the liver. Science 190:794, 1975.PubMedCrossRefGoogle Scholar
  3. Baraona, E., Leo, M., Borowsky, S.A. and Lieber, C. S.: Pathogenesis of alcohol-induced accumulation of protein in the liver. J. Clin. Invest. 60:546, 1977.PubMedCentralPubMedCrossRefGoogle Scholar
  4. Baumgartner, H. P. and Filippini, L.: Alkoholinduzierte Hyperlipoproteinamien. Schweiz. Med. Wschr. 107:1406, 1977.PubMedGoogle Scholar
  5. Borowsky, S. A., Perlow, W., Baraona, E. and Lieber, C. S.: Disappearance of alcoholic hyperlipemia as a sign of advancing liver damage. Gastroenterology 70:978, 1976.Google Scholar
  6. Cachera, R., Lamotte, M. and Lamotte-Barrillon, S.: Etude clinique, biologique et histologique des steatoses du foie chez alcooliques. Semaine Hop., Paris 26:3497, 1950.PubMedGoogle Scholar
  7. Cederbaum, A. L, Lieber, C. S. and Rubin, E.: Effects of chronic ethanol treatment on mitochondrial functions. Arch. Biochem. Biophys. 165:560, 1974a.PubMedCrossRefGoogle Scholar
  8. Cederbaum, A. L, Lieber, C. S. and Rubin, E.: The effect of acetaldehyde on mitochondrial ftmction. Arch. Biochem. Biophys. 161 16, 1974b.CrossRefGoogle Scholar
  9. Cederbaum, A. L, Lieber, C. S., Beattie, D. S. and Rubin, E.: Effect of chronic ethanol ingestion on fatty acid oxidation by hepatic mitochondria. J. Biol. Chem. 250:5122, 1975a.PubMedGoogle Scholar
  10. Cederbaum, A. L, Lieber, C. S. and Rubin, E.: Effect of acetaldehyde on fatty acid oxidation and ketogenesis by hepatic mitochondria. Arch. Biochem. Biophys. 169:29, 1975b.PubMedCrossRefGoogle Scholar
  11. Dajani, R. M. and Kouyoumjian, C.: A probable direct role of ethanol in the pathogenesis of fat infiltration in the rat. J. Nutr. 91:535, 1967.PubMedGoogle Scholar
  12. Dajani, R. M., Danielski, J. and Orten, J. M.: The utilization of ethanol. XL The alcohol-acetaldehyde dehydrogenase systems in the livers of alcohol-treated rats. J. Nutr. 80:196, 1963.PubMedGoogle Scholar
  13. Eriksson, C. J. P.: Ethanol and acetaldehyde metabolism in rat strains genetically selected for their ethanol preference. Biochem. Pharmacol. 22:2283, 1973.PubMedCrossRefGoogle Scholar
  14. Eriksson, C. J. P., Lindros, K. O. and Forsander, O. A.: 2.4-Dinitrophenol- increase in ethanol and acetaldehyde oxidation in the perfused rat liver. Biochem. Pharmacol. 23:2193–2195, 1974.PubMedCrossRefGoogle Scholar
  15. Feinman, L., Baraona, E., Matsuzaki, S., Korsten, M. and Lieber, C. S.: Concentration dependence of ethanol metabolism in vivo in rats and man Alcoholism: Clin. Exper. Res. 2:381, 1978.CrossRefGoogle Scholar
  16. Freimd, G. and O’Hollaren, P.: Acetaldehyde concentrations in alveolar air following a standard dose of ethanol in man. lipid Res. 6:471, 1965.Google Scholar
  17. Greenfield, N. J., Pietruszko, R., Lin, G. and Lester, D.: The effect of ethanol ingestion on the aldehyde dehydrogenases of rat liver. Biochim. Biophys. Acta 428:627, 1976.PubMedCrossRefGoogle Scholar
  18. Grunnet, N., Quistorff, B. and Thieden, H. L D.: Rate-limiting factors in ethanol oxidation by isolated rat liver parenchymal cells. Eur. J.Biochem. 40:175, 1973.CrossRefGoogle Scholar
  19. Hasumura, Y., Teschke, R. and Lieber, C. S.: Acetaldehyde oxidation by hepatic mitochondria. Decrease after chronic ethanol consumption. Science 189:727, 1975.PubMedCrossRefGoogle Scholar
  20. Hasxmitira, Y., Teschke, R. and Lieber, C. S.: Characteristics of acetaldehyde oxidation in rat liver mitochondria. J. Biol. Chem. 251: 4908, 1976.Google Scholar
  21. Horton, A. A.: Induction of aldehyde dehydrogenase in a mitochondrial fraction. Biochim. Biophys. Acta 253:514, 1971.PubMedCrossRefGoogle Scholar
  22. Horton, A. A. and Barrett, M. C.: Rates of induction of mitochondrial aldehyde dehydrogenase in rat liver. Biochem. J. 156:177, 1976.PubMedGoogle Scholar
  23. Iseri, O. A, Lieber, C. S. and Gottlieb, L. S.: The ultrastructure of fatty liver induced by prolonged ethanol ingestion. Amer. J. Path. 48:535, 1966.PubMedGoogle Scholar
  24. Ishii, H., Joly, J-G. and Lieber, C. S.: Effect of ethanol on the amount and enzjrme activities of hepatic rough and smooth microsomal membranes. Biochim. Biophys. Acta 291:411–420, 1973.PubMedCrossRefGoogle Scholar
  25. Kesaniemi, Y. A.: Metabolism of ethanol and acetaldehyde in intact rats during pregnancy. Biochem. Pharmacol. 23:1157, 1974.PubMedCrossRefGoogle Scholar
  26. Koga, S. and Hirayama, C.: Disturbed release of lipoprotein from ethanol induced fatty liver. Experientia 24:438, 1968.PubMedCrossRefGoogle Scholar
  27. Koivula, T. and Lindros, K. O.: Effects of long term ethanol treatment on aldehyde and alcohol dehydrogenase activities in rat liver. Biochem. Pharmacol. 24:1937, 1975.PubMedCrossRefGoogle Scholar
  28. Korsten, M. A., Matsuzaki, S., Feinman, L. and Lieber, C. S.: High blood acetaldehyde levels after ethanol administration in alcoholics. New Eng. J. Med. 292:386, 1975.PubMedCrossRefGoogle Scholar
  29. Lane, B. P. and Lieber, C. S.: Ultrastructural alterations in human hepatocytes following ingestion of ethanol with adequate diets. Amer. J. Pathol 49:593, 1966.Google Scholar
  30. Lieber, C. S.: Metabolism of ethanoL öi Metabolic Aspects of Alcoholism. (C. S. Lieber, ed.). University Park Press, Baltimore, Maryland, Chapter 1, p. 1, 1977.Google Scholar
  31. Lieber, C. S. and DeCarli, L. M.: Reduced nicotinamide-adenine dinucleotide phosphate oxidase: Activity enhanced by ethanol consumption. Science 170:78, 1970a.PubMedCrossRefGoogle Scholar
  32. Lieber, C. S. and DeCarli, L. M.: Quantitative relationship between the amount of dietary fat and the severity of the alcoholic fatty liver. Amer. J. Clin. Nutr. 23:474, 1970b.PubMedGoogle Scholar
  33. Lieber, C. S. and DeCarli, L. M.: The role of the hepatic microsomal ethanol oxidizing system (MEOS) for ethanol metabolism in vivo. J. Pharmacol. Exp. Ther. 181:279, 1972.PubMedGoogle Scholar
  34. Lieber, C. S. and DeCarli, L. M.: An experimental model of alcohol feeding and liver injury in the baboon. J. Med. Primatol. 3:153, 1974.PubMedGoogle Scholar
  35. Lieber, C. S. and Rubin, E.: Alcoholic fatty Hver in man on a high protein and low fat diet. Amer. J. Med. 44:200, 1968.PubMedCrossRefGoogle Scholar
  36. Lieber, C. S., Jones, D. P., Mendelson, J. and DeCarli, L. M.: Fatty liver, hyperlipemia and holeruricemia produced by prolonged alcohol consimiption, despite adequate dietary intake. Trans. Ass. Amer. Physicians 76:289, 1963.Google Scholar
  37. Lieber, C. S., Lefevre, A., Spritz, N., Feinman, L. and DeCarli, L. M.: Difference in hepatic metabolism of long and medium-chain fatty acids: The role of fatty acid chain length in the production of the alcoholic fatty liver. J. Clin. Invest. 46:1451, 1967.PubMedCentralPubMedCrossRefGoogle Scholar
  38. Lindros, K. O.: Acetaldehyde oxidation and its role in the overall metabolic effects of ethanol in the liver; in regulation of hepatic metabolism. In Proceedings of the Alfred Benson Symposium VI, Copenhagen 1973. (F. Limdquist and N. Tygstrup, eds.) p. 417, Copenhagen:Munksgaard, 1974.Google Scholar
  39. Lindros, K. O., Koivula, T. and Eriksson, C. J. P.: Acetaldehyde levels during ethanol oxidation: A diet-induced change and its relation to liver aldehyde dehydrogenases and redox states. Life Sei. 17:1589, 1975CrossRefGoogle Scholar
  40. Losowsky, M. S., Jones, D. P., Davidson, C. S. and Lieber, C. S.: Studies of alcoholic hyperlipemia and its mechanism. Amer. J. Med. 35:794, 1963.PubMedCrossRefGoogle Scholar
  41. Madsen, N. P.: Reduced serum very low-density lipoprotein levels after acute ethanol administration. Biochem. Pharmacol 18:261, 1969.PubMedCrossRefGoogle Scholar
  42. Magrinat, G., Dolan, J. P., Biddy, R. L., Miller, L. D. and Korol, B.: Ethanol and methanol metabolites in alcohol withdrawal. Nature Lond 244:234, 1973.PubMedCrossRefGoogle Scholar
  43. Majchrowicz, E. and Mendelson, J. H.: Blood concentrations of acetal- dehyde and ethanol in chronic alcoholics. Science 168:1100, 1970.PubMedCrossRefGoogle Scholar
  44. Marjanen, L.: Intracellular localization of aldehyde dehydrogenase in rat liver. Biochem. J. 127:633, 1972.PubMedGoogle Scholar
  45. Marzo, A., Ghirardi, P., Sardini, D., Prandini, D. and Albertini, A.: Serum lipids and total fatty acids in chronic alcoholic liver disease at different stages of cell damage. Heft Unfallheilk 48:949, 1970.Google Scholar
  46. Matsuda, Y., Baraona, E., Salaspuro, M. and Lieber, C. S.: Pathogenesis and role of microtubular alterations in alcohol-induced liver injury. Fed. Proc. 37:402, 1978.Google Scholar
  47. Matsuzaki, S. and Lieber, C. S.: Increased susceptibility of hepatic mitochondria to the toxicity of acetaldehyde after chronic ethanol consumption. Biochem. Biophys. Res. Commun. 75:1059, 1977.PubMedCrossRefGoogle Scholar
  48. Mookerjea, S. and Chow, A.: Impairment of glycoprotein synthesis in acute ethanol intoxication in rats. Biochim. Biophys. Acta 184:83, 1969.PubMedCrossRefGoogle Scholar
  49. Ohnishi, K. and Lieber, C. S.: Reconstitution of the microsom ethanol oxidizing system (MEOS): Qualitative and quantitative changes of cytochrome P-450 after chronic ethanol consumption. J. BioL Chem. 252:7124, 1977.PubMedGoogle Scholar
  50. Parrilla, R., Ohkawa, K., Lindros, K. O., Zimmerman, J. P., Kopayashe, K. and Williamson, J. R.: Fimctional compartmentation of acetaldehyde oxidation in rat liver. J. Biol. Chem. 249:4926, 1974.PubMedGoogle Scholar
  51. Raskin, N. H. and Sokoloff, L.: Ethanol-induced adaptation of alcohol dehydrogenase activity in rat brain. Nature Lond. 236:138, 1972.Google Scholar
  52. Redmond, G. and Cohen, G.: Induction of liver acetaldehyde dehydrogenase: Possible role in ethanol tolerance after exposure to barbiturates. Science (Washidon) 171:387, 1971.CrossRefGoogle Scholar
  53. Salaspuro, M. and Lieber, C. S.: Non-ADH pathway of alcoholic metabolism: Its increase in activity at high ethanol concentrations and after chronic consumption. Gastroenterology 73:1244, 1977.Google Scholar
  54. Stowell, A. R., Greenway, R. M. and Batt, R. D.: Acetaldehyde formation during deproteinization of human blood samples containing ethanol. Biochem. Med. 18:392, 1977.PubMedCrossRefGoogle Scholar
  55. Teschke, R., Matsuzaki, S., Ohnishi, K., DeCarli, L. M. and Lieber, C. S.: Microsomal ethanol oxidizing system (MEOS): Current status of its characterization and its role. AlcohoUsm: Clin. Exper. Res. 1:7, 1977.CrossRefGoogle Scholar
  56. Theorell, H. and Bonnichsen, R.: Studies on liver alcohol dehydrogenase. Acta Chem. Scand. 5:1105, 1951.CrossRefGoogle Scholar
  57. Tottmar, S.O. C., Pettersson, H. and Kiessling, K.-H.: The subcellular distribution and properties of aldehyde dehydrogenases in rat liver. J. Biochem. (Tokyo) 135:577, 1973.Google Scholar
  58. Tottmar, S. O. C., Kiessling, K. H. and Forsling, M.: Effects of phenobarbital and ethanol on rat liver aldehyde dehydrogenases. Acta Pharmacol. Toxicol. 35:270, 1974.CrossRefGoogle Scholar
  59. Truitt, E. B.: Blood acetaldehyde levels after alcohol consumption by alcoholics and nonalcoholic subjects. IN Biological Aspects of Alcohol. (M. K. Roach, W. M. Mclsaac and P. J. Creaven, eds.), p. 212, Austin and London: University of Texas Press, 1971.Google Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • C. S. Lieber
    • 1
  • E. Baraona
    • 1
  • Y. Matsuda
    • 1
  • M. Salaspuro
    • 1
  • Y. Hasumura
    • 1
  • S. Matsuzaki
    • 1
  1. 1.Alcoholism Research and Treatment CenterBronx Veterans Hospital and Mt. Sinai School of Medicine of the City University of New YorkN.Y.USA

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