Modulation of thioacetamide-induced hepatocellular necrosis by prostaglandins is associated with novel histologic changes

Authors

  • Nora V. Bergasa,

    Corresponding author
    1. Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases
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  • Maria J. Borque,

    1. Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases
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  • Larry M. Wahl,

    1. Cellular Immunology Section, Laboratory of Immunology, National Institute of Dental Research; National Institutes of Health, Bethesda, Maryland
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  • Lionel Rabin,

    1. Department of Hepatic and Gastrointestinal Pathology, Veterans Administration Reference Laboratory, Armed Forces Institute of Pathology, Washington, D.C., U.S.A.
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  • E. Anthony Jones

    1. Liver Diseases Section, Digestive Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases
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Liver Diseases Section, Building 10; 4-D 52 National Institutes of Health, Bethesda, MD 20892, USA

Abstract

Abstract: Cytoprotective effects of the prostaglandins 16, 16-dimethyl PGE2 (dmPGE2) and PGF2 α tromethamine (PGF2 α) were evaluated in the rat model of acute hepatocellular necrosis induced by thioacetamide (TAA). dmPGE2 (100 μg/kg SC 8 hourly) did not induce a significant increase in survival when started after the onset of TAA-induced fulminant hepatic failure. However, priming with dmPGE2 (100 μg/kg SC 30 min before TAA) reduced TAA-induced elevations in serum ALT (684 ± 68 (SEM) vs 274 ± 135 IU/1, p>0.01). This phenomenon did not occur if dmPGE2 was administered after TAA or by the IP route. Modulation of TAA-induced centrizonal hepatocellular necrosis by dmPGE2 was associated with a striking increase in centrizonal ballooning of hepatocytes (p>0.01), and, as assessed by stereology, less hepatocellular necrosis and degenerative changes. PGF2 α, which in contrast to dmPGE2 does not act via cAMP, had no effect on TAA-induced changes in serum ALT or hepatic histology. These findings suggest that dmPGE2 decreases hepatocellular necrosis by activating surface membrane adenylate cyclase and consequently stimulating cAMP. Ballooning of hepatocytes could occur secondary to these membrane events and appears to be a marker of dmPGE2-induced cytoprotection in this model.

The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

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