Hepatocellular Metabolism of 4-Hydroxy-2,3-Nonenal Is Impaired in Conditions of Chronic Cholestasis

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 hep...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1995-09, Vol.214 (2), p.669-675
Main Authors: Leonarduzzi, G., Parola, M., Muzio, G., Garramone, A., Maggiora, M., Robino, G., Poli, G., Dianzani, M.U., Canuto, R.A.
Format: Article
Language:English
Subjects:
Alcohol Dehydrogenase - metabolism
Aldehydes - metabolism
Animals
Bile Ducts - physiology
Cholestasis - metabolism
Glutathione Transferase - metabolism
Kinetics
Lipid Peroxidation
Liver - metabolism
Male
NAD - metabolism
NADP - metabolism
Rats
Rats, Wistar
Reference Values
Subcellular Fractions - enzymology
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Summary: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.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1995.2338