New prolyl 4-hydroxylase inhibitor reduces procollagen gene expression and enzyme-altered lesions in rat liver cirrhosis

J Gastroenterol Hepatol. 1995:10 Suppl 1:S63-4. doi: 10.1111/j.1440-1746.1995.tb01801.x.

Abstract

A choline deficient L-amino acid defined (CDAA) diet led to the development of liver cirrhosis in male Wistar rats after 16 weeks. A new prolyl 4-hydroxylase inhibitor, 2,4-pyridine dicarboxylic acid bis [(2-methoxyethyl amide)] (HOE 077), prevented liver fibrosis in a dose-dependent manner without a reduction in increased serum alanine aminotransferase and aspartate aminotransferase in parallel with a reduction in preneoplastic enzyme-altered lesions stained with anti-glutathione S-transferase placental form antibody. HOE 077 reduced the increase in serum procollagen III peptide (PIIIP) in a dose-dependent manner and in proportion to the reduction in mRNA expression of type III procollagen in the liver of rats fed a CDAA diet.

MeSH terms

  • Alanine Transaminase / blood
  • Animals
  • Aspartate Aminotransferases / blood
  • Blotting, Northern
  • Choline / administration & dosage
  • Diet
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Gene Expression / drug effects
  • Liver / metabolism
  • Liver Cirrhosis, Experimental / enzymology
  • Liver Cirrhosis, Experimental / metabolism*
  • Male
  • Procollagen / genetics*
  • Procollagen / metabolism
  • Procollagen-Proline Dioxygenase / antagonists & inhibitors*
  • Pyridines / pharmacology*
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar

Substances

  • Enzyme Inhibitors
  • Procollagen
  • Pyridines
  • RNA, Messenger
  • lufironil
  • Procollagen-Proline Dioxygenase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Choline