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 peroxi dation known to exert several biological and cytotoxic effects and to be produced during conditions of chronic cholestasis. Here we report t hat viable hepatocytes isolated from cholestatic livers of bile duct-l igated rats (BDL hepatocytes) show a significantly lower rate of HNE m etabolism than control cells. This feature is likely to be the consequ ence of a significant inhibition in the activity of HNE-metabolizing c ytosolic glutathione-S-transferase and alcohol dehydrogenase In BDL he patocytes. Particulate NADP-dependent aldehyde dehydrogenase was also inhibited. No significant change was found for aldehyde reductase acti vity. A decreased hepatocellular metabolism of HNE can expose liver pa renchymal and non-parenchymal cells to cytotoxic as well as proinflamm atory and pro-fibrogenic effects of HNE, contributing to the developme nt of chronic cholestatic liver damage. (C) 1995 Academic Press, Inc.