Fibrosis accelerates the development of enzyme-altered lesions in the rat liver.
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.
Sakaida
I
I
First Department of Internal Medicine, School of of Medicine, Yamaguchi University, Kogushi Ube, Yamaguchi-Pref., Japan. sakaida@po.cc.yamaguchi-u.ac.jp
Hironaka
K
K
Uchida
K
K
Suzuki
C
C
Kayano
K
K
Okita
K
K
D000199:Actins / Q000032:analysis / Q000235:genetics; D000596:Amino Acids / Q000008:administration & dosage; D000818:Animals; D001769:Blood; D002794:Choline / Q000008:administration & dosage; D004032:Diet; D005982:Glutathione Transferase / Q000032:analysis; D006909:Hydroxyproline / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D011230:Precancerous Conditions; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D013552:Swine
D000199:Actins; D000596:Amino Acids; D012333:RNA, Messenger; D008315:Malondialdehyde; D005982:Glutathione Transferase; D002794:Choline; D006909:Hydroxyproline