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

✍ Scribed by Kenji Fujiwara; Itsuro Ogata; Yasuhiko Ohta; Shigeki Hayashi; Shunji Mishiro; Katsuyoshi Takatsuki; Yuzuru Sato; Shinwa Yamada; Keichi Hirata; Hiroshi Oka; Toshitsugu Oda; Hisanori Kawaji; Shinobu Matsuda; Yasuhiko Niiyama; Ryoichi Tsukuda

• Publisher: John Wiley and Sons
• Year: 1988
• Tongue: English
• Weight: 461 KB
• Volume: 8
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840080418

✦ Synopsis

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-l894B, 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.