Severe and progressive steatosis and focal necrosis in rat liver induced by continuous intragastric infusion of ethanol and low fat diet

Authors

  • Hidekazu Tsukamoto D.V.M.,

    Corresponding author
    1. Veterans Administration Medical Center, Martinez, California 94553
    2. Departments of Internal Medicine, Pathology and Biological Chemistry, School of Medicine, University of California, Davis, California 95616
    • Research Service, Veterans Administration Medical Center, 150 Muir Road, Martinez, California 94553
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  • Samuel W. French,

    1. Veterans Administration Medical Center, Martinez, California 94553
    2. Departments of Internal Medicine, Pathology and Biological Chemistry, School of Medicine, University of California, Davis, California 95616
    Current affiliation:
    1. Department of Pathology, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada KIN 9A9
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  • Nancy Benson,

    1. Veterans Administration Medical Center, Martinez, California 94553
    2. Departments of Internal Medicine, Pathology and Biological Chemistry, School of Medicine, University of California, Davis, California 95616
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  • George Delgado,

    1. Veterans Administration Medical Center, Martinez, California 94553
    2. Departments of Internal Medicine, Pathology and Biological Chemistry, School of Medicine, University of California, Davis, California 95616
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  • G. Ananda Rao,

    1. Veterans Administration Medical Center, Martinez, California 94553
    2. Departments of Internal Medicine, Pathology and Biological Chemistry, School of Medicine, University of California, Davis, California 95616
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  • Edward C. Larkin,

    1. Veterans Administration Medical Center, Martinez, California 94553
    2. Departments of Internal Medicine, Pathology and Biological Chemistry, School of Medicine, University of California, Davis, California 95616
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  • Corey Largman

    1. Veterans Administration Medical Center, Martinez, California 94553
    2. Departments of Internal Medicine, Pathology and Biological Chemistry, School of Medicine, University of California, Davis, California 95616
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Abstract

Blood alcohol levels (BAL) were maintained at high levels (overall mean ± S.D. achieved in 14 alcoholic rats was 216.0 ± 120.1 mg%) in male Wistar rats for 15 to 85 days by continuous intragastric infusion of ethanol and nutritionally defined low fat liquid diet. The ethanol intake was progressively increased from 32% of total calories up to 41.4% in order to maintain high BAL. Pair-fed animals received isocaloric glucose solution and the liquid diet. Despite the low level of dietary fat (4.9% of total calories), histopathological evaluation of the liver revealed severe and progressive fatty infiltration in the alcoholic rats. In addition, following 30 days of intoxication, one third of the animals showed focal necrosis with mononuclear cell infiltration in centrilobular areas of the livers. This was correlated with the markedly elevated levels of SGOT and SGPT in these animals. Pair-fed controls showed no abnormality in the morphology of liver or blood chemistry. Chemical quantitation of liver triglycerides confirmed the histological observation, with triglyceride levels of 61.51 ± 16.45 and 89.61 ± 5.94 mg per gm at 30 and 85 days, respectively. Most importantly, the degree of steatosis was tightly and significantly correlated with the mean BAL achieved (r = 0.80, p < 0.001). These data represent the first confirmation of the hypothesis that continuously high BAL correlate with the severity of alcohol-induced liver pathology.

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