Alterations of specific forms of cytochrome P-450 in rat liver during acute carbon tetrachloride intoxication
| Autor: | C. H. Woo, Bobbie Head, Edward A. Smuckler, David E. Moody |
|---|---|
| Rok vydání: | 1981 |
| Předmět: |
Male
Cytochrome Toxicology Mixed Function Oxygenases chemistry.chemical_compound Cytochrome P-450 Enzyme System medicine Animals Heme Pharmacology Gel electrophoresis Oxidase test biology Carbon Tetrachloride Poisoning Rats Inbred Strains Molecular biology Rats chemistry Biochemistry Carbon tetrachloride biology.protein Microsome Microsomes Liver Phenobarbital Benzphetamine NADP medicine.drug |
| Zdroj: | Toxicology and applied pharmacology. 61(2) |
| ISSN: | 0041-008X |
| Popis: | Male rats were pretreated with phenobarbital, 3-methylcholanthrene, or the corresponding vehicles, administered carbon tetrachloride (CCl4), and sacrificed 3 hr later. Hepatic microsomes were isolated and assayed for cytochrome P-450 content and mixed-function oxidase activity. The residual content of cytochrome P-450 after CCl4 intoxication was similar in saline and phenobarbital-pretreated animals. Substantially greater amount of cytochrome P-450 remained in animals pretreated with 3-methylcholanthrene and then challenged with CCl4. In saline-pretreated animals, the dealkylation of 7-ethoxycoumarin, but not benzphetamine or N,N-dimethylaniline, was decreased following CCl4 exposure. The enhanced dealkylation following phenobarbital, but not following by 3-methylcholanthrene, was also decreased after CCl4 poisoning. Microsomes were solubilized with sodium cholate; cytochrome P-450 was partially purified by ω-octylamino Sepharose 4B column chromatography; and cytochrome P-450-containing elements were separated by SDS-polyacrylamide gel electrophoresis. A decrease in the staining intensity of a band migrating with a molecular weight of 51,600 was noted following CCl4 treatment. Furthermore, the phenobarbital-induced component (MW 51,600), but not that appearing after 3-methylcholanthrene induction (MW 57,900), was also diminished. Microsomal proteins separated by SDS-polyacrylamide gel electrophoresis and stained for heme also showed a decrease in staining which was greater in those microsomal proteins from phenobarbital and saline than in 3-methylcholanthrene-induced animals. The data suggest that a specific cytochrome P-450(s) in the saline-treated animals as well as the cytochrome P-450(s) induced by phenobarbital, but not the 3-methylcholanthrene-induced cytochrome P-450, are susceptible to CCl4-induced destruction. |
| Databáze: | OpenAIRE |
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