Hepatic Fibrosis After Long-Term Administration of Ethanol and Moderate Vitamin A Supplementation in the Rat

Authors

  • Maria Anna Leo,

    Corresponding author
    1. Alcohol Research and Treatment Center, and Section of Liver Disease and Nutrition, Bronx Veterans Administration Medical Center and Mount Sinai School of Medicine, New York, New York 10029
    • M. A. Leo, M.D., Alcohol Research and Treatment Center, Veterans Administration Medical Center, 130 West Kingsbridge Road, Bronx, New York 10468.
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    • Dr. Leo is a recipient of a NIADDK Clinical Investigator Award AM-69801.

  • Charles S. Lieber

    1. Alcohol Research and Treatment Center, and Section of Liver Disease and Nutrition, Bronx Veterans Administration Medical Center and Mount Sinai School of Medicine, New York, New York 10029
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  • This work was also presented in part at the Annual Meeting of the American Association for the Study of Liver Diseases, Chicago, Illinois, November 1981 and published in abstract form (Hepatology 1981; 1:520).

Abstract

Rats were fed up to 9 months diets supplemented with vitamin A in an amount that, by itself, had no apparent adverse effect on the liver. When associated with chronic ethanol administration, vitamin A supplementation strikingly exacerbated ethanol-induced abnormalities: fat accumulation was increased and numerous giant mitochondria were observed. Furthermore, lesions appeared which ethanol alone does not produce in rats, namely necrosis, inflammation, and fibrosis. Vitamin A supplementation increased the number of fat storing cells (lipocytes) which positively correlated with vitamin A accumulation in the liver. However, when vitamin A supplementation was combined with ethanol administration, vitamin A levels in the liver and the number of fat storing cells decreased and numerous myofibroblasts appeared in association with abundant collagen fibers. There was also hepatic inflammation and necrosis, accompanied by a rise in serum glutamate dehydrogenase, SGOT, and SGPT and a decrease in retinol binding protein and vitamin A. We conclude that amounts of vitamin A, which by themselves appear harmless, may produce severe liver lesions when associated with chronic ethanol consumption.

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