title: Decreased collagen accumulation by a prolyl hydroxylase inhibitor in pig serum-induced fibrotic rat liver.
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.
authors.affiliation: First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Fujiwara
authors.forename: I
authors.initials: I
authors.lastname: Ogata
authors.forename: Y
authors.initials: Y
authors.lastname: Ohta
authors.forename: S
authors.initials: S
authors.lastname: Hayashi
authors.forename: S
authors.initials: S
authors.lastname: Mishiro
authors.forename: K
authors.initials: K
authors.lastname: Takatsuki
authors.forename: Y
authors.initials: Y
authors.lastname: Sato
authors.forename: S
authors.initials: S
authors.lastname: Yamada
authors.forename: K
authors.initials: K
authors.lastname: Hirata
authors.forename: H
authors.initials: H
authors.lastname: Oka
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000494:pharmacology*; D001769:Blood; D003094:Collagen / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008106:Liver Cirrhosis, Experimental / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors*; D011392:Proline / Q000378:metabolism; D051381:Rats; D013552:Swine
chemical_list: D000880:Anthraquinones; C032958:vineomycin A1; D003094:Collagen; D011392:Proline; D011393:Procollagen-Proline Dioxygenase; D006909:Hydroxyproline