Comparative Effects of Chloroflavone Congeners as Inducers of Hepatic Microsomal Monooxygenases in Rats
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概要
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The inductive effects of pretreatment with 10 synthetic chloroflavone isomers and congeners (80 mg/kg/d for 3 d, i.p.) on hepatic microsomal monooxygenases were examined with male Wistar rats. All chloroflavone congeners, except 3'-chloroflavone (CF), significantly increased (1.2-to 2-fold) the content of total cytochrome P-450 (P-450s) in microsomes. The effects of these congeners were evaluated based on the activities of microsomal aminopyrine N-demethylase, aniline hydroxylase and scoparone (6,7-dimethoxycoumarin) O-demethylase, and the CO difference spectrum and sodium dodecyl sulfate-gel electrophoretogram of cytochrome P-450s. The results were compared with those of phenobarbital (PB), 3-methylcholanthrene (MC) and PB plus MC. Based mainly on effects on the CO difference spectrum and ratio of the two O-demethylase activities of scoparone, 2'-CF and 2', 4'-dichloroflavone (DCF) were categorized as the PB-type, 4'-CF and 6,8-DCF as the MC-type, 3', 6-DCF and 3', 5', 6-trichloroflavone as weak MC-type, and 6-CF and 2', 6-DCF as mixed (PB plus MC)-type inducers. A comparison of chloroflavone isomers and congeners indicated that (1) the presence of the 2'-chloro substituent of the flavone system is a minimal requirement for exhibiting the PB-type effect, (2) the absence of the 2'-chloro substituent is possibly that for exhibiting the MC-type effect and (3) the induction potencies by individual chloroflavone congeners may not be related to the degrees of chlorination.
- 公益社団法人日本薬学会の論文
著者
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Kato Sachiko
School Of Pharmacy Hokuriku University
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YAMAMOTO KAZUMITSU
Research and Development Division, Dainippon Pharmaceutical Co., Ltd.
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YAMAMOTO KENJI
School of Pharmacy Hokuriku University
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Yamamoto Kazuo
東京大学 新領域創成科研究
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Yamamoto Kazuo
Laboratory Of Molecular Medicine Department Of Integrated Biosciences Graduate School Of Frontier Sc
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