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

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.