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Effects of inhibitors of RNA and protein synthesis on hepatic microsomal cytochrome P-450 concentration in fasted and fed rats.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 1985 Oct 15; Vol. 34 (20), pp. 3661-5. - Publication Year :
- 1985
-
Abstract
- A number of sex-related differences in the metabolism of drugs, steroids and xenobiotics have been reported in studies on rats. Generally, male rats tend to metabolize these compounds more efficiently than females. In the studies presented here, male and female rats were fasted for 24-48 hr, and the effects of fasting on total hepatic microsomal cytochrome P-450 were examined. Hepatic cytochrome P-450, as determined by CO difference spectra, was increased significantly as a percentage of control in microsomes from fasted female rats when compared to fasted male rats. Cytochrome P-450 concentration increased from 0.57 +/- 0.07 nmole/mg protein to 0.99 +/- 0.08 nmole/mg protein following a 24-hr fast. In male rats, cytochrome P-450 levels were essentially unaffected by the 24-hr fast. Cytochrome b5 concentration was not altered by fasting. When female rats were fasted for 24 hr and refed, cytochrome P-450 levels were not significantly different from cytochrome P-450 levels in continuously fed animals. Treatment of fasted female rats with the protein synthesis inhibitor ethionine, or the RNA synthesis inhibitor actinomycin D, prevented the induction of cytochrome P-450 in the fasting animal. Cytochrome P-450 concentration in fed animals was not affected significantly by either inhibitor. Induction of cytochrome P-450 by phenobarbital (PB) and 3-methylcholanthrene (MC) under fed and fasted conditions was also investigated in male and female rats. Xenobiotic-induced cytochrome P-450 concentration was significantly higher in fasted female hepatic microsomes when compared to microsomes from fed female rats. Fasting did not significantly affect xenobiotic-induced cytochrome P-450 in male rats. Our results suggest that fasting in female rats results in an increase in cytochrome P-450 which is dependent upon synthesis of RNA and protein.
- Subjects :
- Animals
Cytochrome P-450 Enzyme System analysis
Cytochrome b Group analysis
Cytochrome b Group biosynthesis
Dactinomycin pharmacology
Enzyme Induction drug effects
Ethionine pharmacology
Female
Injections, Intraperitoneal
Male
Microsomes, Liver drug effects
Microsomes, Liver metabolism
Rats
Rats, Inbred Strains
Sex Factors
Cytochrome P-450 Enzyme System biosynthesis
Food Deprivation physiology
Microsomes, Liver enzymology
RNA biosynthesis
Subjects
Details
- Language :
- English
- ISSN :
- 0006-2952
- Volume :
- 34
- Issue :
- 20
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 2413863
- Full Text :
- https://doi.org/10.1016/0006-2952(85)90227-8