Abstract
Isolated stellate cell on plastic dish indicated the proliferation and the expression of procollagen type I mRNA during 14 days culture. Thus culture system of stellate cell in vitro may reflect pathophysiology in vivo. A choline deficient L-amino acid defined (CDAA) diet led to the development of liver cirrhosis in 100% of male Wistar rats after 16 weeks and developed hepatocellular carcinoma in 90% of rats after one year. Concurrent administration of a prolyl 4-hydroxylase inhibitor, 2, 4-pyridine dicarboxylic acid bis [(2-methoxyethyl amide)] (HOE 077), to rats fed a CDAA diet reduced the increase in liver hydroxyproline content in a dose-dependent manner for doses up to 200ppm in parallel with the percent area of GSTP-positive lesions. Also 200ppm HOE 077 reduced the incidence of development of hepatocellular carcinoma from 90% to 50% one year after a CDAA diet administration. These data suggest that inhibition of fibrosis may limit the development of subsequent neoplasms in the liver.
