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Hepatocellular metabolism of 4-hydroxy-2,3-nonenal is impaired in conditions of chronic cholestasis.

Abstract：

:4-Hydroxy-2,3-nonenal is a major aldehydic end-product of lipid peroxidation known to exert several biological and cytotoxic effects and to be produced during conditions of chronic cholestasis. Here we report that viable hepatocytes isolated from cholestatic livers of bile duct-ligated rats (BDL hepatocytes) show a significantly lower rate of HNE metabolism than control cells. This feature is likely to be the consequence of a significant inhibition in the activity of HNE-metabolizing cytosolic glutathione-S-transferase and alcohol dehydrogenase in BDL hepatocytes. Particulate NADP-dependent aldehyde dehydrogenase was also inhibited. No significant change was found for aldehyde reductase activity. A decreased hepatocellular metabolism of HNE can expose liver parenchymal and non-parenchymal cells to cytotoxic as well as pro-inflammatory and pro-fibrogenic effects of HNE, contributing to the development of chronic cholestatic liver damage.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Leonarduzzi G,Parola M,Muzio G,Garramone A,Maggiora M,Robino G,Poli G,Dianzani MU,Canuto RA

doi

10.1006/bbrc.1995.2338

subject

Has Abstract

pub_date

1995-09-14 00:00:00

pages

669-75

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(85)72338-8

journal_volume

214

pub_type

杂志文章

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