The integrated value of serum procollagen III peptide over time predicts hepatic hydroxyproline content and stainable collagen in a model of dietary cirrhosis in the rat

Authors

  • Mary J. Ruwart Ph.D.,

    Corresponding author
    1. Diabetes and Gastrointestinal Diseases Research and Biostatistics, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Department of Internal Medicine (Gastroenterology) and Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109
    3. Department of Internal Medicine (Gastroenterology), Steglitz Medical School, Berlin, Federal Republic of Germany
    • Drug Delivery Systems Research, The Upjohn Company, Kalamazoo, Michigan 49001
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  • Karen F. Wilkinson,

    1. Diabetes and Gastrointestinal Diseases Research and Biostatistics, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Department of Internal Medicine (Gastroenterology) and Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109
    3. Department of Internal Medicine (Gastroenterology), Steglitz Medical School, Berlin, Federal Republic of Germany
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  • Bob D. Rush,

    1. Diabetes and Gastrointestinal Diseases Research and Biostatistics, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Department of Internal Medicine (Gastroenterology) and Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109
    3. Department of Internal Medicine (Gastroenterology), Steglitz Medical School, Berlin, Federal Republic of Germany
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  • Thomas J. Vidmar,

    1. Diabetes and Gastrointestinal Diseases Research and Biostatistics, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Department of Internal Medicine (Gastroenterology) and Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109
    3. Department of Internal Medicine (Gastroenterology), Steglitz Medical School, Berlin, Federal Republic of Germany
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  • Kenneth M. Peters,

    1. Diabetes and Gastrointestinal Diseases Research and Biostatistics, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Department of Internal Medicine (Gastroenterology) and Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109
    3. Department of Internal Medicine (Gastroenterology), Steglitz Medical School, Berlin, Federal Republic of Germany
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  • Keith S. Henley,

    1. Diabetes and Gastrointestinal Diseases Research and Biostatistics, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Department of Internal Medicine (Gastroenterology) and Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109
    3. Department of Internal Medicine (Gastroenterology), Steglitz Medical School, Berlin, Federal Republic of Germany
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  • Henry D. Appelman,

    1. Diabetes and Gastrointestinal Diseases Research and Biostatistics, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Department of Internal Medicine (Gastroenterology) and Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109
    3. Department of Internal Medicine (Gastroenterology), Steglitz Medical School, Berlin, Federal Republic of Germany
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  • Kiyoung Y. Kim,

    1. Diabetes and Gastrointestinal Diseases Research and Biostatistics, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Department of Internal Medicine (Gastroenterology) and Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109
    3. Department of Internal Medicine (Gastroenterology), Steglitz Medical School, Berlin, Federal Republic of Germany
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  • Detlef Schuppan,

    1. Diabetes and Gastrointestinal Diseases Research and Biostatistics, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Department of Internal Medicine (Gastroenterology) and Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109
    3. Department of Internal Medicine (Gastroenterology), Steglitz Medical School, Berlin, Federal Republic of Germany
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  • Eckert G. Hahn

    1. Diabetes and Gastrointestinal Diseases Research and Biostatistics, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Department of Internal Medicine (Gastroenterology) and Department of Pathology, University of Michigan, Ann Arbor, Michigan 48109
    3. Department of Internal Medicine (Gastroenterology), Steglitz Medical School, Berlin, Federal Republic of Germany
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Abstract

To determine whether a serum parameter of collagen metabolism, serum procollagen type III peptide, correlated with hepatic collagen in a model of diet-induced fibrosis, rats were fed a control or cirrhogenic diet for 6 months and treated with either subcutaneous vehicle or the hepatoprotective prostaglandin 16,16-dimethyl prostaglandin E2 (100 μg per kg) twice daily. Pair-fed rats from each group were killed after 2, 4 or 6 months. The value of serum procollagen type III peptide to body weight integrated over time (Kt) correlated linearly with hepatic hydroxyproline content (r = 0.97) at killing time t. Good correlations were also seen between Kt and histopathological assessment of aniline blue-stainable collagen (r = 0.93) and between the histopathology and hydroxyproline content (r = 0.97). Rats receiving 16,16-dimethyl prostaglandin E2 had lower values of all three parameters compared to rats receiving vehicle, confirming the previously demonstrated hepatoprotective effect of 16,16-dimethyl prostaglandin E2. The excellent correlation between Kt and the two other traditional parameters of hepatic collagen suggest that sequential measurements of serum procollagen type III peptide can be used to predict alterations in liver collagen deposition in rats.

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