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An in vitro model of ethanol‐dependent liver cell injury
Author(s) -
Lamb Robert G.,
Koch John C.,
Snyder Jack W.,
Huband Shiva M.,
Bush Suzanne R.
Publication year - 1994
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840190127
Subject(s) - viability assay , ethanol , biosynthesis , biochemistry , phospholipid , chemistry , phosphatidylcholine , lipid peroxidation , liver cell , metabolism , medicine , endocrinology , in vitro , biology , antioxidant , enzyme , membrane
Primary cultures of adult rat hepatocytes were incubated (6 to 96 hr) with 50 to 150 mmol/L ethanol, 0.5 mmol/L linoleate, 0.5 mmol/L palmitate, 0.5 mmol/L 4‐methylpyrazole, 0 to 25 μmol/L vitamin E phosphate or selected combinations of these agents. Agent‐dependent changes in liver cell viability (AST release and reduction of 3‐(4,5‐dimethylthiazol‐2‐yl)−2,5‐diphenyltetrazolium bromide) and function (phospholipid peroxidation, hydrolysis, biosynthesis and triacylglycerol biosynthesis) were determined. The influence of ethanol on liver cell function and viability was dose and incubation time dependent. Short periods (24 hr or less) of exposure to 100 mmol/L ethanol increased liver cell triacylglycerol biosynthesis and phospholipid hydrolysis, peroxidation and biosynthesis without altering cell viability. However, longer periods (72 hr or more) of exposure to 100 or 150 mmol/L ethanol resulted in significant reductions (30 to 50) in cell viability, function and phosphatidylcholine biosynthesis and content. The ethanol‐dependent decreases in cell function and viability were potentiated by linoleate and reduced by vitamin E phosphate, palmitate and 4‐methylpyrazole. These results suggest that ethanol‐induced liver cell injury in vitro is not a result of ethanol per se , but factors such as acetaldehyde or oxyradicals produced as a consequence of ethanol metabolism. Therefore the incubation of cultured hepatocytes with ethanol may be an appropriate model in vitro for determining the mechanisms by which ethanol intake disrupts liver cell function in vivo . (Hepatology 1994;19:174–182).