Ethanol and drug metabolism in mouse liver microsomes subsequent to lipid peroxidation-induced destruction of cytochrome P-450 |
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Authors: | K P Vatsis J A Kowalchyk M P Schulman |
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Institution: | Dept. of Pharmacology, University of Illinois College of Medicine, Chicago, IL 60612 USA |
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Abstract: | Preincubation of mouse liver microsomes with NADPH resulted in malondialdehyde formation, destruction of cytochrome P-450, and decreased rates of aniline hydroxylation and N-demethylation of aminopyrine and ethylmorphine. These phenomena were more pronounced in phosphate than in Tris buffer. No reduction in rates of NADPH-linked oxidation of ethanol or in the activities of NADPH oxidase and NADPH-cytochrome c reductase was observed. While addition of EDTA to preincubation mixtures prevented lipid peroxidation, loss of cytochrome P-450, and inactivation of the drug-metabolizing capacity of microsomes, it did not alter ethanol oxidation rates and the activities of NADPH oxidase and NADPH-cytochrome c reductase. These findings argue against the involvement of cytochrome P-450 in the microsomal ethanol-oxidizing system. |
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