EFFECTS OF BIOFLAVONOIDS ON HEPATIC P450 ACTIVITIES

被引：125

作者：

OBERMEIER, MT ^{[1
]}

WHITE, RE ^{[1
]}

YANG, CS ^{[1
]}

机构：

[1] RUTGERS STATE UNIV,COLL PHARM,DEPT CHEM BIOL & PHARMACOGNOSY,CANC RES LAB,PISCATAWAY,NJ 08855

来源：

XENOBIOTICA | 1995年 / 25卷 / 06期

关键词：

D O I：

10.3109/00498259509061876

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

1. The effects of tangeretin, green tea flavonoids, and other flavonoids on 7-ethoxyresorufin-O-deethplase (EROD; 450 1A), 7-pentoxyresorufin-O-dealkylase (PROD; P450 2B), P-nitrophenol hydroxylase (PNPH, P450 2E1), and erythromycin-N-demethylase (ERDM; P450 3A) were examined in induced rat liver microsomes. EROD, PNPH, ERDM, and nifedipine oxidase (NIFO; P450 3A4) were examined in human liver microsomes. 2. All flavonoids tested inhibited EROD activity at higher concentrations in liver microsomes. Flavone and tangeretin were potent inhibitors of EROD, with IC50's of 0.7 and 0.8 mu M respectively in rat liver microsomes and 0.15 and 16 mu M respectively in human liver microsomes. The green tea flavonoid (-)-epicatechin-3-gallate (EGG) was the most potent inhibitor of EROD in human liver microsomes (IC50 = 75 mu M). The effect of the green tea flavonoids on EROD was complex; in addition to inhibition at high concentrations of flavonoid, moderate activation was seen at lower concentrations. 3. 450 2B-, 2E1- and 3A-dependent activities in rat and human liver microsomes were only moderately inhibited by any of the flavonoids tested, and, in general, ECG was the most potent inhibitor for these activities with IC50's ranging from 75 to 300 mu M. 4. Tangeretin inhibited EROD activity (P450 1A2) in human liver microsomes in a competitive manner with a K-i = 68 nM. Tangeretin inhibited NIFO activity (P450 3A4) inhuman liver microsomes in an uncompetitive manner with K-i = 72 mu M.

引用

页码：575 / 584

页数：10

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