Further Differentiation of 2'- and 4'-Chloroflavones as Inducers of Hepatic Microsomal Monooxygenases in Rats

2'-Chloroflavone (CF) and 4'-CF were studied as inducers of cytochrome P-450-mediated monooxygenases in rat hepatic microsomes by comparison with phenobarbital (PB) and 3-methylcholanthrene (MC). As a result of interaction with the substrate 7-ethoxycoumarin (7-EC), 2'-CF-induced micr...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 1993/01/15, Vol.16(1), pp.90-92
Main Authors: KATO, Sachiko, YAMAMOTO, Kenji
Format: Article
Language:English
Subjects:
2'-chloroflavone
4'-chloroflavone
7-Alkoxycoumarin O-Dealkylase - biosynthesis
Aminopyrine N-Demethylase - biosynthesis
Animals
Biological and medical sciences
Cytochrome P-450 Enzyme System - biosynthesis
Enzyme Induction - drug effects
Flavonoids - pharmacology
General pharmacology
inducer type
Male
Medical sciences
Methylcholanthrene - pharmacology
Microsomes, Liver - drug effects
Microsomes, Liver - enzymology
monooxygenase induction
Oxidoreductases, O-Demethylating - biosynthesis
Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions
Pharmacology. Drug treatments
Phenobarbital - pharmacology
rat liver microsome
Rats
Rats, Wistar
selective inhibitor
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Summary:2'-Chloroflavone (CF) and 4'-CF were studied as inducers of cytochrome P-450-mediated monooxygenases in rat hepatic microsomes by comparison with phenobarbital (PB) and 3-methylcholanthrene (MC). As a result of interaction with the substrate 7-ethoxycoumarin (7-EC), 2'-CF-induced microsomes showed a difference spectrum different from usual type I, whereas 4'-CF-induced microsomes showed a typical type I spectrum. 2'-CF-induced microsomes increased the Vmax of aminopyrine (AM) N-demethylase activity about 1.6-fold while not affecting the apparent Km value. In contrast, 4'-CF-induced microsomes decreased the Km of 7-EC O-deethylase activity to about one fourth while significantly increasing the Vmax value. All the activities of AM N-demethylase, 7-EC O-deethylase and 6, 7-dimethoxycoumarin O-demethylase in 2'-CF-induced microsomes were inhibited strongly by metyrapone and SKF 525-A, and significantly by diphenhydramine. The three enzyme activities in 4'-CF-induced microsomes were inhibitied markedly by α-naphthoflavone and significantly by 2-bromo-4'-nitroacetophenone. These results further support the previous proposal that 2'-CF is a PB-type inducer of cytochrome P-450 while 4'-CF is a MC-type inducer.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.16.90