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

• Published in: Hepatology (Baltimore, Md.) Vol. 8; no. 4; p. 804
• Main Authors: Fujiwara, K, Ogata, I, Ohta, Y, Hayashi, S, Mishiro, S, Takatsuki, K, Sato, Y, Yamada, S, Hirata, K, Oka, H
• Format: Journal Article
• Language: English
• Published: United States 01.07.1988
• Subjects: 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
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840080418

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.