Alcohol-mediated effects on the level of cytochrome P-450 and heme biosynthesis in cultured rat hepatocytes |
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Authors: | Stanley E. Lane M.Elizabeth Stewart |
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Affiliation: | Division of Biomedical Sciences, Meharry Medical College, Nashville, TN, 37208, U.S.A. |
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Abstract: | Interaction of alcohol and drugs in the liver appears to involve common microsomal oxidative enzymes which utilize cytochrome P-450. Since alcohol augments the toxicity of a variety of drugs, the regulation of the P-450 hemoprotein, a primary component in hepatic drug metabolizing systems, may play a vital role in this phenomenon. We utilize an adult rat liver culture system as a model to explore the action of levels of alcohol below that which is necessary to produce intoxication in humans. The addition of 16 mM ethanol (70 mg/dl) to these hepatocytes results in a 49.5% decrease in cytochrome P-450 activity after 24 h, and a 3-fold increase in the activity of δ-aminolevulinate synthase, the rate-limiting enzyme in hepatic heme biosynthesis. Furthermore, ethanol treatment also causes a transient decrease in the level of intracellular heme. However, the diminished level of total heme does not appear to act as a repressor for δ-aminolevulinate synthase, since it occurs after the initial stimulation of the enzyme by ethanol. |
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Keywords: | Ethanol Cytochrome P-450 Heme synthesis Aminolevulinate synthase (Rat hepatocyte) |
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