Role of acetaldehyde in the ethanol-induced impairment of hepatic glycoprotein secretion in the rat In vivo

✍ Scribed by Gary D. Volentine; Kathleen A. Ogden; David K. Kortje; Dean J. Tuma; Michael F. Sorrell

• Publisher: John Wiley and Sons
• Year: 1987
• Tongue: English
• Weight: 607 KB
• Volume: 7
• Category: Article
• ISSN: 0270-9139
• DOI: 10.1002/hep.1840070313

✦ Synopsis

Ethanol administration inhibits hepatic protein and glycoprotein secretion. Previous studies have shown that the metabolism of ethanol is required for this effect. Experiments were designed to determine whether acetaldehyde, the first metabolite of ethanol oxidation, mediated the ethanol-induced secretory defect in rats with normal and stimulated (inflammation-induced) rates of hepatic protein secretion. This study used cyanamide, an aldehyde dehydrogenase inhibitor, to correlate enhanced acetaldehyde levels with an increased ethanolinduced inhibition of hepatic protein secretion. Inflammation was induced by turpentine 24 hr prior to cyanamide (5 mg per kg body weight) or saline pretreatment. Nonfasted rats were intragastrically gavaged with ethanol (4 to 6 gm per kg body weight) or isocaloric glucose 1 hr following pretreatment. [%I]Fucose and/or ["Clleucine were injected intravenously 2 hr following intubation. With elevated levels of acetaldehyde, the ethanol-induced impairment of secretion of labeled proteins and their parallel retention in the liver were markedly potentiated.During inflammation, this inhibition of secretion by ethanol was maintained and further increased with cyanamide pretreatment. These results indicate that the ethanol-induced impairment of hepatic glycoprotein secretion is mediated by acetaldehyde in both normal and inflammation-stimulated animals.

The production of plasma proteins is a major specialized function of the liver, representing a considerable fraction of the total protein synthetic activity of the hepatocyte (1, 2). Plasma proteins are the major secretory proteins of the liver and are composed of albumin, a nonglycosylated protein, and numerous glycoproteins (3-5). Albumin and the peptide moiety of glycoproteins are synthesized on membrane-bound polysomes and are vectorially discharged into the cisternae of the endoplas-