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
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.