16,16-dimethyl prostaglandin E2 delays collagen formation in nutritional injury in rat liver

Authors

  • Mary J. Ruwart Ph.D.,

    Corresponding author
    1. Diabetes and Gastrointestinal Diseases Research, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Departments of Internal Medicine (Gastroenterology) and Pathology, The University of Michigan, Ann Arbor, Michigan
    • 7241–25–10, Diabetes and Gastrointestinal Diseases Research, Kalamazoo, Michigan 49001
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  • Bob D. Rush,

    1. Diabetes and Gastrointestinal Diseases Research, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Departments of Internal Medicine (Gastroenterology) and Pathology, The University of Michigan, Ann Arbor, Michigan
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  • Karen F. Snyder,

    1. Diabetes and Gastrointestinal Diseases Research, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Departments of Internal Medicine (Gastroenterology) and Pathology, The University of Michigan, Ann Arbor, Michigan
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  • Ken M. Peters,

    1. Diabetes and Gastrointestinal Diseases Research, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Departments of Internal Medicine (Gastroenterology) and Pathology, The University of Michigan, Ann Arbor, Michigan
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  • Henry D. Appelman,

    1. Diabetes and Gastrointestinal Diseases Research, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Departments of Internal Medicine (Gastroenterology) and Pathology, The University of Michigan, Ann Arbor, Michigan
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  • Keith S. Henley

    1. Diabetes and Gastrointestinal Diseases Research, The Upjohn Company, Kalamazoo, Michigan 49001
    2. Departments of Internal Medicine (Gastroenterology) and Pathology, The University of Michigan, Ann Arbor, Michigan
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  • This work was presented in part at the meeting of the AGA/AASLD, New York, New York, 1985.

Abstract

Chronic nutritional injury was induced in rats by a high-fat, lipotrope-deficient diet. The hepatoprotective effect of 16,16-dimethyl prostaglandin E2 on the deposition of collagen and fat was assessed by histological evaluation and measurement of hydroxyproline. Dose-response studies established that optimal protection was achieved by the twice daily administration of 16,16-dimethyl prostaglandin E2 at 100 μg per kg (subcutaneous) or 250 μg per kg (oral). 16,16-Dimethyl prostaglandin E2 and a crystalline analog [(p-acetami-dobenzamido)phenyl ester of 16,16-dimethyl prostaglandin E2 significantly delayed both the deposition of collagen and the increase in hepatic hydroxyproline content. There was an excellent correlation between the histological assessment of collagen and the biochemical measurement of hydroxyproline. These data provide a rationale for the evaluation of prostaglandins in the treatment of human liver disease.

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