HETEROGENOUS EFFECTS OF NATURAL FLAVONOIDS ON MONOOXYGENASE ACTIVITIES IN HUMAN AND RAT-LIVER MICROSOMES

被引：111

作者：

SIESS, MH ^{[1
]}

LECLERC, J ^{[1
]}

CANIVENCLAVIER, MC ^{[1
]}

RAT, P ^{[1
]}

SUSCHETET, M ^{[1
]}

机构：

[1] UNIV BOURGOGNE, CTR HOSP REG, SERV CHIRURG VISCERALE, F-21033 DIJON, FRANCE

来源：

TOXICOLOGY AND APPLIED PHARMACOLOGY | 1995年 / 130卷 / 01期

关键词：

D O I：

10.1006/taap.1995.1010

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The in vitro effects of nine flavonoids on different monooxygenase activities from human and rat liver were investigated. Flavonoids belonging to different chemical classes [flavones (chrysin, tangeretin, flavone, 5,6-benzoflavone, 7,8-benzoflavone), flavonols (quercetin), and flavanones (pinocembrin, eriodictyol, flavanone)] were chosen. Ethoxyresorufin O-deethylase (EROD) and benzyloxyresorufin O-debenzylase (BROD) were selected as marker activities of P450 isoenzymes involved in carcinogen activation. Human EROD activity was inhibited by all flavonoids. Flavonoids without hydroxyl groups were more effective than those with hydroxyl groups. Flavonoids with an unsaturated flavane nucleus were more inhibitory than the corresponding saturated analogues. Similar structure-activity relationships were found in microsomes from methylcholanthrene-treated rats. The effects of flavonoids on human BROD activity were quite different from those observed on EROD activity. Nonhydroxylated flavones were effective activators. Hydroxylated flavonoids showed a biphasic effect, being activators at low concentrations and inhibitors at higher concentrations. The effects of flavonoids on BROD activity were rather similar in man and control rats. (C) 1995 Academic Press, Inc.

引用

页码：73 / 78

页数：6

共 31 条

[1] GRAPEFRUIT JUICE FELODIPINE INTERACTION - MECHANISM, PREDICTABILITY, AND EFFECT OF NARINGIN [J].

BAILEY, DG ;

ARNOLD, JMO ;

MUNOZ, C ;

SPENCE, JD .

CLINICAL PHARMACOLOGY & THERAPEUTICS, 1993, 53 (06) :637-642

[2] FLAVONOIDS AS INHIBITORS OF RAT-LIVER MONOOXYGENASE ACTIVITIES [J].

BEYELER, S ;

TESTA, B ;

PERRISSOUD, D .

BIOCHEMICAL PHARMACOLOGY, 1988, 37 (10) :1971-1979

[3]

BUENING MK, 1981, CANCER RES, V41, P67

[4] ETHOXYPHENOXAZONES, PENTOXYPHENOXAZONES, AND BENZYLOXYPHENOXAZONES AND HOMOLOGS - A SERIES OF SUBSTRATES TO DISTINGUISH BETWEEN DIFFERENT INDUCED CYTOCHROMES-P-450 [J].

BURKE, MD ;

THOMPSON, S ;

ELCOMBE, CR ;

HALPERT, J ;

HAAPARANTA, T ;

MAYER, RT .

BIOCHEMICAL PHARMACOLOGY, 1985, 34 (18) :3337-3345

[5] HUMAN CYTOCHROME P-450PA (P-450IA2), THE PHENACETIN O-DEETHYLASE, IS PRIMARILY RESPONSIBLE FOR THE HEPATIC 3-DEMETHYLATION OF CAFFEINE AND N-OXIDATION OF CARCINOGENIC ARYLAMINES - (AROMATIC-AMINES HETEROCYCLIC AMINES CARCINOGEN METABOLISM) [J].

BUTLER, MA ;

IWASAKI, M ;

GUENGERICH, FP ;

KADLUBAR, FF .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (20) :7696-7700

[6] EFFECTS OF SYNTHETIC AND NATURALLY-OCCURRING FLAVONOIDS ON BENZO[A]PYRENE METABOLISM BY HEPATIC MICROSOMES PREPARED FROM RATS TREATED WITH CYTOCHROME-P-450 INDUCERS [J].

CHAE, YH ;

MARCUS, CB ;

HO, DK ;

CASSADY, JM ;

BAIRD, WM .

CANCER LETTERS, 1991, 60 (01) :15-24

[7]

DIGIOVANNI J, 1990, CHEM CARCINOGENESIS, P159

[8] RELATIVE EXPRESSION OF CYTOCHROME P450 ISOENZYMES IN HUMAN LIVER AND ASSOCIATION WITH THE METABOLISM OF DRUGS AND XENOBIOTICS [J].

FORRESTER, LM ;

HENDERSON, CJ ;

GLANCEY, MJ ;

BACK, DJ ;

PARK, BK ;

BALL, SE ;

KITTERINGHAM, NR ;

MCLAREN, AW ;

MILES, JS ;

SKETT, P ;

WOLF, CR .

BIOCHEMICAL JOURNAL, 1992, 281 :359-368

[9] FLAVONE MODULATORS OF RAT HEPATIC ARYL-HYDROCARBON HYDROXYLASE [J].

FRIEDMAN, FK ;

WEST, D ;

SUGIMURA, T ;

GELBOIN, HV .

PHARMACOLOGY, 1985, 31 (04) :203-207

[10] INHIBITORY EFFECT OF GRAPEFRUIT JUICE AND ITS BITTER PRINCIPAL, NARINGENIN, ON CYP1A2 DEPENDENT METABOLISM OF CAFFEINE IN MAN [J].

FUHR, U ;

KLITTICH, K ;

STAIB, AH .

BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 1993, 35 (04) :431-436

← 1 2 3 4 →