Fibrosis accelerates the development of enzyme-altered lesions in the rat liver.

Abstract

Injection of pig serum into rats twice a week for 8 weeks induced stellate cell activation resulting in liver fibrosis without parenchymal cell injury. Administration of a choline deficient L-amino acid defined (CDAA) diet for 6 weeks with or without pig serum pretreatment led to the development of preneoplastic lesions that were positive for the placental form of glutathione S-transferase (GSTP). Pig serum pretreatment induced more activated stellate cells in the livers of rats subsequently fed a CDAA diet for 6 weeks compared with rats fed the CDAA diet alone. Activated stellate cells were detected as smooth muscle actin (SMA)-positive cells and by the expression of SMA messenger RNA. These cells caused severe fibrosis as assessed by the hepatic hydroxyproline content. Pre-existing fibrosis induced by the activation of stellate cells with pig serum pretreatment increased hepatic malondialdehyde (MDA) level in parallel with GSTP-positive lesions. These results indicate that pre-existing fibrosis with the activated stellate cells accelerates the development of preneoplastic lesions in a CDAA diet model.

• Authors: I Sakaida, K Hironaka, K Uchida, C Suzuki, K Kayano, K Okita
• Journal: Hepatology (Baltimore, Md.) (Hepatology) Vol. 28 Issue 5 Pg. 1247-52 (Nov 1998) ISSN: 0270-9139 [Print] United States
• PMID: 9794908 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Actins
• Amino Acids
• RNA, Messenger
• Malondialdehyde
• Glutathione Transferase
• Choline
• Hydroxyproline

Topics

• Actins (analysis, genetics)
• Amino Acids (administration & dosage)
• Animals
• Blood
• Choline (administration & dosage)
• Diet
• Glutathione Transferase (analysis)
• Hydroxyproline (analysis)
• Liver (chemistry, enzymology, metabolism)
• Liver Cirrhosis, Experimental (enzymology, etiology, pathology)
• Liver Neoplasms (etiology)
• Male
• Malondialdehyde (metabolism)
• Precancerous Conditions
• RNA, Messenger (analysis)
• Rats
• Rats, Wistar
• Swine