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.
Fujiwara
K
K
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Ogata
I
I
Ohta
Y
Y
Hayashi
S
S
Mishiro
S
S
Takatsuki
K
K
Sato
Y
Y
Yamada
S
S
Hirata
K
K
Oka
H
H
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
D000880:Anthraquinones; C032958:vineomycin A1; D003094:Collagen; D011392:Proline; D011393:Procollagen-Proline Dioxygenase; D006909:Hydroxyproline