Inhibition of Hepatic Microsomal Cytochrome P450 by Cannabidiol in Adult Male Rats
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概要
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The mechanism of inhibitory effect of cannabidiol (CBD) on the hepatic drug-metabolizing enzyme system was studied in adult male rats in vivo. Time course studies revealed that microsomal d-benzphetamine N-demethylation and testosterone 2α-, 16α- and 17-oxidation were markedly suppressed 6 to 48h after the single administration of CBD (10mg/kg, intraperitoneally). Decreases in activities of aniline hydroxylation and p-nitroanisole O-demethylation and in content of total cytochrome P450 were intermittent and moderate. On the other hand, no change was observed in reduced nicotinamide adenine dinucleotide phosphate (NADPH)-cytochrome c reductase activity or cytochrome b_5 content in the hepatic microsomes of the CBD-treated rats. Western blotting analysis showed a marked decrease in the male-specific cytochrome P450 UT-2 in the hepatic microsomes, especially 24 to 48h after pretreatment with CBD. It is possible that CBD given 6 to 12h before the sacrifice might interact with cytochrome P450 as a substrate, resulting in inhibition of the drug-metabolizing enzyme activities in the earlier stages. In the later stages from 24 to 48h after CBD treatment, the reduction in content of the male-specific cytochrome P450 UT-2 may play a major role in the inhibitory effect of CBD on the hepatic drug-metabolizing enzyme system in the adult male rat in vivo.
- 公益社団法人日本薬学会の論文
- 1990-05-25
著者
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舩江 良彦
大阪市立北市民病院 麻酔科
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今岡 進
大阪市立北市民病院 麻酔科
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成松 鎮雄
千葉大・薬
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今岡 進
Laboratory of Chemistry, Osaka City University Medical School
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成松 鎮雄
岡山大・薬・衛生化学
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成松 鎭雄
Laboratory Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University
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吉村 英敏
Faculty Of Pharmaceutical Sciences Kyushu University
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松永 民秀
北陸大学薬学部衛生化学教室
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松永 民秀
Faculty of Pharmaceutical Sciences, Hokuriku University
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渡辺 和人
Faculty of Pharmaceutical Sciences, Hokuriku University
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山本 郁男
Faculty of Pharmaceutical Sciences, Hokuriku University
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船江 良彦
Laboratory Of Chemistry Osaka City University Medical School
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舩江 良彦
Laboratory of Chemistry, Osaka City University Medical School
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成松 鎭雄
Faculty of Pharmaceutical Sciences, Hokurku University
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山本 郁男
Faculty Of Pharmaceutical Sciences Kumamoto University
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Yoshida H
Lab. Of Food & Nutritional Sciences Dep. Of Nutritional Sci. Kobe-gakuin Univ.
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Narimatsu S
Laboratory Of Biopharmaceutics Faculty Of Pharmaceutical Sciences Chiba University
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