New prolyl 4-hydroxylase inhibitor reduces procollagen gene expression and enzyme-altered lesions in rat liver cirrhosis.
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.
Sakaida
I
I
First Department of Internal Medicine, Yamaguchi University, Japan.
Okita
K
K
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015152:Blotting, Northern; D002794:Choline / Q000008:administration & dosage; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D008099:Liver / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D011347:Procollagen / Q000235:genetics* / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D011347:Procollagen; D011725:Pyridines; D012333:RNA, Messenger; C074630:lufironil; D011393:Procollagen-Proline Dioxygenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002794:Choline