Decreased collagen accumulation by a prolyl hydroxylase inhibitor in pig serum-induced fibrotic rat liver

Hepatology. 1988 Jul-Aug;8(4):804-7. doi: 10.1002/hep.1840080418.

Abstract

Hepatic fibrosis was induced in rats by repeated i.p. injections of pig serum. The hepatic hydroxyproline content increased to 2.1 times the normal control level at 6 weeks and to 3.2 times at 10 weeks. When P-1894B, an inhibitor of prolyl hydroxylase, was administered, there was a dose-dependent inhibition of the increase to nearly normal control levels at 6 and 10 weeks. There was also by histology a dose-dependent reduction in the degree of hepatic fibrosis. Hepatocellular damage was minimal and its extent did not vary with the degree of fibrosis or the treatment. P-1894B dose dependently reduced the hydroxylation of peptidyl proline in the fibrotic liver. These data suggest that P-1894B inhibited hepatic fibrogenesis by direct action on collagen but not by protection against hepatocellular damage leading to collagen formation. A prolyl hydroxylase inhibitor may be a candidate for use in treatment of hepatic fibrosis.

MeSH terms

  • Animals
  • Anthraquinones / pharmacology*
  • Blood
  • Collagen / metabolism*
  • Dose-Response Relationship, Drug
  • Hydroxyproline / metabolism
  • Liver / metabolism*
  • Liver / pathology
  • Liver Cirrhosis, Experimental / etiology
  • Liver Cirrhosis, Experimental / metabolism*
  • Liver Cirrhosis, Experimental / pathology
  • Male
  • Procollagen-Proline Dioxygenase / antagonists & inhibitors*
  • Proline / metabolism
  • Rats
  • Swine

Substances

  • Anthraquinones
  • vineomycin A1
  • Collagen
  • Proline
  • Procollagen-Proline Dioxygenase
  • Hydroxyproline