ON THE ROLE OF LIPID-PEROXIDATION IN THE PATHOGENESIS OF LIVER-DAMAGEINDUCED BY LONG-STANDING CHOLESTASIS

Citation
M. Parola et al., ON THE ROLE OF LIPID-PEROXIDATION IN THE PATHOGENESIS OF LIVER-DAMAGEINDUCED BY LONG-STANDING CHOLESTASIS, Free radical biology & medicine, 20(3), 1996, pp. 351-359
Citations number
61
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biology
ISSN journal
0891-5849
Volume
20
Issue
3
Year of publication
1996
Pages
351 - 359
Database
ISI
SICI code
0891-5849(1996)20:3<351:OTROLI>2.0.ZU;2-O
Abstract
Previous studies have suggested a possible involvement of free radical reactions in the pathogenesis of cholestatic liver injury as well as in the modulation of hepatic fibrogenesis. In this study we investigat ed whether lipid peroxidation is involved in the development of chroni c liver damage induced by long-standing cholestasis. For this purpose we have used the rat model of bile duct ligation (BDL), which leads to liver fibrosis and cirrhosis. Using this model we observed that the d evelopment of chronic liver damage was associated with the onset of li pid peroxidation, as pointed out by detection of carbonyl compounds, 4 -hydroxynonenal (HNE) and malondialdehyde (MDA), in BDL livers and of fluorescent adducts between MDA and serum proteins. Lipid peroxidation was a relatively late event (starting after 1-2 weeks of BDL) and was unrelated to the early development of liver necrosis and cholestasis (already evident after 72 h after BDL). A positive significant linear correlation between the kinetic of infiltration of neutrophils and of a monocyte/macrophage population in BDL livers and MDA and HNE generat ion in the same organs is presented, indicating a close link between l ipid peroxidation and the activation of inflammatory cells. We also ob served that a positive linear correlation exists between collagen depo sition in these livers and hepatic production of MDA and HNE. This eve nt, which is accompanied by an increase in the number of fat storing c ells (FSC, the cells that produce collagen in fibrotic liver), suggest s that lipid peroxidation in this model may contribute to stimulate co llagen synthesis by proliferating FSC.