CHRONIC ETHANOL ADMINISTRATION IMPAIRS DEGRADATION OF FORMALDEHYDE-TREATED ALBUMIN BY THE PERFUSED-RAT-LIVER

Nonparenchymal cells of the liver appear to be important in the pathog enesis of various liver diseases, including that caused by ethanol. It is known that chronic ethanol administration impairs the process of r eceptor-mediated endocytosis in hepatocytes. Liver endothelial cells a re also actively endocytic cells, playing a prominent role in the clea rance from the circulation of a variety of macromolecules. In this stu dy, we assessed the effect of ethanol administration on this ''scaveng er'' function of liver endothelial cells by measuring the degradation of formaldehyde-treated albumin in isolated, perfused livers of ethano l-fed rats. Rats were pair-fed for 1 or 4 weeks with a liquid diet con taining either ethanol as 36% of total calories or an isocaloric amoun t of carbohydrate. Chronic ethanol administration in this manner for 1 or 4 weeks significantly impaired the degradation of this endothelial cell ligand (by 60 +/- 9% and 37 +/- 9%, respectively). Liver perfusi ons were also performed an rats that had been administered ethanol acu tely or in which ethanol was added to the perfusate. No acute effect o f ethanol on the degradation of this ligand was seen. These results de monstrate that chronic ethanol ingestion impairs receptor-mediated end ocytosis of formaldehyde-treated albumin by liver endothelial cells, i ndicating that the adverse effects of ethanol on protein trafficking w ithin the river are not limited to the hepatocytes.