Alcoholic Liver Injury: Experimental Models in Rats and Baboons

  • Charles S. Lieber
  • Leonore M. DeCarli
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 59)


A model has been developed for the administration to rats and baboons of ethanol as part of a nutritionally adequate liquid diet. With this regimen, ethanol intake was much higher than with conventional procedures. All animals gained or maintained their body weight, and liver morphology was normal in the controls. Isocaloric substitution of carbohydrate by ethanol (36% of total calories in rats and 50% in baboons) resulted in the production of fatty liver in all animals, while the baboons also developed alcoholic hepatitis and cirrhosis with increased activities of serum glutamic oxaloacetic transaminase. Inebriation and manifestation of dependence upon withdrawal of the diet were observed in baboons and quantitated in the rat. Chemical alterations produced by ethanol at the fatty liver stage were characterized by hyperlipemia, striking triglyceride accumulation in the liver and enhanced activities of microsomal drug metabolizing enzymes, including the microsomal ethanol oxidizing system (MEUS). Ultrastructural changes of the mitochondria and the endoplasmic reticulum were already present at the fatty liver stage and persisted throughout the hepatitis and cirrhosis. The lesions were similar to those observed in alcoholics (including the inflammation and the central sclerosis), and differed strikingly from the alterations produced by other models of liver injury. In showing that all aspects of liver injury observed in alcoholics can be reproduced in animals by the feeding of pure ethanol with an adequate diet, this study incriminates ethanol itself as a cause for the hepatic complications. This new experimental model is proposed as a tool for the study of the pathogenesis and treatment of alcoholic liver injury and dependence.


Liver Injury Fatty Liver Liquid Diet Ethanol Intake Alcoholic Hepatitis 
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. Baraona, E. and Lieber, C.S. 1970, J. Clin. Invest. 49:769. Baraona, E., Pirola, R.C. and Lieber, C.S. 1973, J. Clin. Invest. 52: 296.Google Scholar
  2. Best, C.H., Hartroft, W.S., Lucas, C.C. and Ridout, J.H. 1949, Brit. Med. J. ii: 1001.Google Scholar
  3. Bonnichsen, R. Methods of Enzymatic Analysis, edited by H.U. Bergmeyer, New York, Academic Press, 1963, p. 285.Google Scholar
  4. DeCarli, L.M. and Lieber, C.S. 1967, J. Nutr. 91:331. Feinman, L. and Lieber, C.S. 1972, Science 176: 795.Google Scholar
  5. Foy, H., Kondi, A. and Mbaya, V. 1964, Brit. J. Nutr. 18:307, Hoffbauer, F.W. and Zaki, F.G. 1965, Arch. Path. 79: 364.Google Scholar
  6. Hummer, R.L. Feeding and Nutrition of Nonhuman Primates, edited by R.S. Harris, New York, Academic Press,1970 p. 183.Google Scholar
  7. Imai, Y., Ito, A. and Sato, R. 1966, J. Biochem. 60: 417.Google Scholar
  8. Iseri, O.A., Lieber, C.S. and Gottlieb, L.S. 1966, Amer. J. Path. 48: 535.Google Scholar
  9. Ishii, H., Joly, J.-G. and Lieber., C.S. 1973, Biochlm. Biophys. Acta 291: 411.Google Scholar
  10. Joly, J.-G., Ishii, H,, Teschke, R., Hasumura, Y. and Lieber, C.S. 1973, Biochem. Pharmacol. 22: 1532.CrossRefGoogle Scholar
  11. Lane, B.P. and Lieber, C.S. 1966, Amer,. J. Path. 49: 593.Google Scholar
  12. Lefevre, A.F., DeCarli, L.M, and Lieber, C.S. 1972, J. Lipid Res. 13: 48.Google Scholar
  13. Lieber, C.S. 1973, New Eng. J. Med. 288: 356.Google Scholar
  14. Lieber, C.S. and DeCarli, L.M. 1968, Science 162: 917.CrossRefGoogle Scholar
  15. Lieber, C.S. and DeCarli, L.M. 1970a, Amer. J. Clin. Nutr. 2.3:474. Lieber, C.S. and DeCarli, L.M. 1970b, J. Biol. Chem. 2.45:9505.Google Scholar
  16. Lieber, C.S. and DeCarli, L.M. 1973, Res. Commun. Chem. Path. Pharmacol. 6: 983.Google Scholar
  17. Lieber, C.S. and DeCarli, L.M. 1974, J. Med. Primatology 3:153. lieber, C.S. and Rubin, E. 1968, Amer. J. Med. 44: 200.Google Scholar
  18. Lieber, C.S., Jones, D.P., Mendelson, T. and DeCarli, L.M. 1963, Trans. Ass, Amer. physicians 76: 289.Google Scholar
  19. Lieber, C,S., Jones, D.P. and DeCarli, L.M. 1965, J. Clin. Invest. 44: 1009.Google Scholar
  20. Lieber, C.S., Spritz, N. and DeCarli, L.M. 1966, J. Clin. Invest. 45: 51.Google Scholar
  21. Lieber, C.S., Lefevre, A., Spritz, N., Feinman, L. and DeCarli, L.M. 1967, J. Clin. Invest. 46: 1451.Google Scholar
  22. Lieber, C.S., Spritz, N. and DeCarli, L.M. 1969, J. Lipid Res. 10: 283.Google Scholar
  23. Lieber, C.S., DeCarli, L.M., Gang, H., Walker, G. and Rubin, E. Medical Primatology-1972. edited by E.I. Goldsmith and J. Moor-Jankowski, Basel, S. Karger, Part 3, 1922, p. 270.Google Scholar
  24. Losowsky, M.S., Jones, D.P., Davidson, C.S. and Lieber, C.S. 1963, New Eng. J. Med. 268: 651.CrossRefGoogle Scholar
  25. Mezey, E. and Tobon, F. 1971, Gastroenterology 61: 707.Google Scholar
  26. Misra, P.S., Lefevre, A., Ishii, H., Rubin, E. and Lieber, C.S. 1971, Amer. J. Med. 51: 346.CrossRefGoogle Scholar
  27. National Research Council. Food and Nutrition Board. Recommended Dietary Allowances. 8th Edition. Washington, D.C. Natl. Acad. Sci. 1974.Google Scholar
  28. Pirola, R.C. and Lieber, C.S. 1972, Pharmacology 7:185Google Scholar
  29. Portman, 0.W. Feeding and Nutrition of Nonhuman Primates. edited by R.S. Harris, New York, Academic Press, 1970, p. 87.Google Scholar
  30. Rubin, E. and Lieber, C.S. 1968a, New Eng. J. Med. 278:869. Rubin, E. and Lieber, C.S. 1968b, Science 162: 690.CrossRefGoogle Scholar
  31. Rubin, E. and Lieber, C.S. 1974, New Eng. J. Med. 290:128. Rubin, E., Hutterer, F. and Lieber, C.S. 1968, Science 159: 1469.CrossRefGoogle Scholar
  32. Ruebner, B.H., Moore, J., Rutherford, R.B., Seligman, A.M. and Zuidema, G.D. 1969, Exp. Molec. Path. 11: 53.Google Scholar
  33. Saville, P.D. and Lieber, C.S. 1965, J. Nutr. 87:477.Google Scholar
  34. Svoboda, D.J. and Manning, R.T. 1964, Amer. J. Path. 44:645.Google Scholar
  35. Wilgram, G.F. 1959, Ann. Intern. Med. 51: 1134.Google Scholar

Copyright information

© Springer Science+Business Media New York 1975

Authors and Affiliations

  • Charles S. Lieber
    • 1
  • Leonore M. DeCarli
    • 1
  1. 1.Laboratory of the Section of Liver Disease and Nutrition, Veterans Administration Hospital, Bronx, New York and Department of MedicineMount Sinai School of Medicine of the City University of New YorkNew YorkUSA

Personalised recommendations