WIF-B cells as a model for alcohol-induced hepatocyte injury

• Published in: Biochemical pharmacology Vol. 67; no. 11; pp. 2167 - 2174
• Main Authors: Schaffert, Courtney S, Todero, Sandra L, McVicker, Benita L, Tuma, Pamela L, Sorrell, Michael F, Tuma, Dean J
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.06.2004; Elsevier Science
• Subjects: Alcohol dehydrogenase; Alcohol Dehydrogenase - metabolism; Aldehyde Dehydrogenase - metabolism; Animals; Biological and medical sciences; Cells, Cultured; Cytochrome P4502E1; Disease Models, Animal; Ethanol - pharmacology; Ethanol metabolism; Hepatocytes - drug effects; Hepatocytes - enzymology; Liver Diseases, Alcoholic - enzymology; Liver Diseases, Alcoholic - pathology; Liver injury; Medical sciences; Pharmacology. Drug treatments; Rats; Triglycerides; WIF-B cells; ALDH; 4-MP; WIF-B cells; ADH; Cytochrome P4502E1; Triglycerides; CYP2E1; Alcohol dehydrogenase; Ethanol metabolism; Liver injury; Ethanol; Digestive system; Enzyme; Toxicity; Liver; Pharmacology; Metabolism; Hepatocyte; Oxidoreductases
• ISSN: 0006-2952; 1873-2968
• DOI: 10.1016/j.bcp.2004.01.022

A potential in vitro model for studying the mechanisms of alcohol-induced hepatocyte injury is the WIF-B cell line. It has many hepatocyte-like features, including a differentiated, polarized phenotype resulting in formation of bile canaliculi. The aim of this study was to examine the effects of ethanol treatment on this cell line. WIF-B cells were cultured up to 96 h in the absence or presence of 25 mM ethanol and subsequently were analyzed for ethanol-induced physiological and morphological changes. Initial studies revealed WIF-B cells exhibited alcohol dehydrogenase (ADH) activity, expressed cytochrome P4502E1 (CYP2E1), and efficiently metabolized ethanol in culture. This cell line also produced the ethanol metabolite acetaldehyde and exhibited low K m aldehyde dehydrogenase (ALDH) activity, comparable to hepatocytes. Ethanol treatment of the WIF-B cells for 48 h led to significant increases in the lactate/pyruvate redox ratio and cellular triglyceride levels. Ethanol treatment also significantly altered WIF-B morphology, decreasing the number of bile canaliculi, increasing the number of cells exhibiting finger-like projections, and increasing cell diameter. The ethanol-induced changes occurring in this cell line were negated by addition of the ADH inhibitor, 4-methylpyrazole (4-MP), indicating the effects were due to ethanol metabolism. In summary, the WIF-B cell line metabolizes ethanol and exhibits many ethanol-induced changes similar to those found in hepatocytes. Because of these similarities, WIF-B cells appear to be a suitable model for studying ethanol-induced hepatocyte injury.