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 pathogenesis of various liver diseases, including that caused by ethanol. It is known that chronic ethanol administration impairs the process of receptor-mediated endocytosis in hepatocytes. Liver endothelial cells are also actively endocytic cells, playing a prominent role in the clearance from the circulation of a variety of macromolecules. In this study, we assessed the effect of ethanol administration on this "scavenger" function of liver endothelial cells by measuring the degradation of formaldehyde-treated albumin in isolated, perfused livers of ethanol-fed rats. Rats were pair-fed for 1 or 4 weeks with a liquid diet containing either ethanol as 36% of total calories or an isocaloric amount 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 perfusions were also performed on rats that had been administered ethanol acutely or in which ethanol was added to the perfusate. No acute effect of ethanol on the degradation of this ligand was seen. These results demonstrate that chronic ethanol ingestion impairs receptor-mediated endocytosis of formaldehyde-treated albumin by liver endothelial cells, indicating that the adverse effects of ethanol on protein trafficking within the liver are not limited to the hepatocytes.
Rees
G M
GM
Liver Study Unit, Omaha Veterans Administration Medical Center, NE 68105.
Miller
J A
JA
Casey
C A
CA
Tuma
D J
DJ
D000818:Animals; D004705:Endocytosis / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D000431:Ethanol / Q000493:pharmacokinetics / Q000633:toxicity*; D005557:Formaldehyde / Q000493:pharmacokinetics*; D008099:Liver / Q000098:blood supply; D008108:Liver Diseases, Alcoholic / Q000503:physiopathology*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D017457:Receptors, Albumin / Q000187:drug effects* / Q000502:physiology; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics*
D017457:Receptors, Albumin; C044105:formaldehyde-serum albumin; C044106:formaldehyde-serum albumin receptor; D005557:Formaldehyde; D012710:Serum Albumin, Bovine; D000431:Ethanol