Comparative effects of flavonoids and model inducers on drug-metabolizing enzymes in rat liver

Canivenc-Lavier, Marie-Chantal; Vernevaut, Marie-France; Totis, Muriel; Siess, Marie‐Hélène; Magdalou, Jacques; Suschetet, Marc

doi:10.1016/s0300-483x(96)03412-9

Cited by 107 publications

(46 citation statements)

References 25 publications

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“…Significantly, such conjugative metabolism does not seem to include reaction with GSH, thus rendering the possibility unlikely that GSH conjugates of quercetin are causally implicated in its putative nephrotoxic potential. In addition, there is no consistent conclusion to the effect of quercetin on cellular GSH levels by quercetin (Nijhoff et al, 1993, CanivencLavier et al, 1996Sahu and Gray, 1996).…”

Section: Discussionmentioning

confidence: 95%

Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity

et al. 2004

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Quercetin (3,5,7,3 0 ,4 0 -pentahydroxyflavone) is a flavone with putative ability to prevent cancer and cardiovascular diseases. Its metabolism was evaluated in rats and human. Rats received quercetin via the intravenous (i.v.) route and metabolites were isolated from the plasma, urine and bile. Analysis was by high-performance liquid chromatography and confirmation of species identity was achieved by mass spectrometry. Quercetin and isorhamnetin, the 3 0 -O-methyl analogue, were found in both the plasma and urine. In addition, several polar peaks were characterised as sulphated and glucuronidated conjugates of quercetin and isorhamnetin. Extension of the metabolism studies to a cancer patient who had received quercetin as an i.v. bolus showed that (Quercetin removed) isorhamnetin and quercetin 3 0 -O-sulphate were major plasma metabolites. As a catechol, quercetin can potentially be converted to a quinone and subsequently conjugated with glutathione (GSH). Oxidation of quercetin with mushroom tyrosinase in the presence of GSH furnished GSH conjugates of quercetin, two mono-and one bis-substituted conjugates. However, these species were not found in biomatrices in rats treated with quercetin. As cyclo-oxygenase-2 (COX-2) expression is mechanistically linked to carcinogenesis, we examined whether quercetin and its metabolites can inhibit COX-2 in a human colorectal cancer cell line (HCA-7). Isorhamnetin and its 4 0 -isomer tamarixetin were potent inhibitors, reflected in a 90% decrease in prostaglandin E-2 (PGE-2) levels, a marker of COX-2 activity. Quercetin was less effective, with a 50% decline. Quercetin 3-and 7-O-sulphate had no effect on PGE-2. The results indicate that quercetin may exert its pharmacological effects, at least in part, via its metabolites. Naturally occurring flavonoids in the diet are associated with several beneficial health effects and understanding the mechanisms underlying these effects has become the focus of much research. Quercetin (3,5,7,3 0 ,4 0 -pentahydroxyflavone, for structure see Figure 1) is a prime example of such a flavonoid. Its glycosylated form occurs in kale, French beans, broccoli, apples and especially in onions, with an abundance as high as a quarter to half a gram per kg (Hertog et al, 1992). On ingestion with the diet, quercetin glycosides are rapidly hydrolysed to generate quercetin.Epidemiological evidence links diets rich in quercetin with decreased incidence of cardiovascular and neoplastic diseases

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Section: Discussionmentioning

confidence: 95%

Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity

et al. 2004

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“…These chemopreventive effects of flavonoids are possibly exerted through a variety of mechanisms, including modification of detoxification enzymes 16,17) and free radical scavenging.…”

Section: Discussionmentioning

confidence: 99%

The Chemopreventive Effect of Taxifolin Is Exerted through ARE-Dependent Gene Regulation

Lee

Hyun

Dangaa³

et al. 2007

Biological & Pharmaceutical Bulletin

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“…Flavonoids exert a multiplicity of biochemical actions that are believed to be an important part of the chemopreventive effect of plant-based diets. Various flavonoids are potent antioxidants (Kono et al, 1997;Noda et al, 1997), inhibit lipoxygenase and cyclooxygenase (Mirzoeva and Calder, 1996), affect the activity of several hepatic enzymes involved in activation and detoxification of carcinogens (Canivenc-Lavier et al, 1996), inhibit cellular proliferation (Tsyrlov et al, 1994;Siess et al, 1995;Moon et al, 1998), and induce apoptosis of tumour cells (Csokay et al, 1997). Galangin, a member of the flavonol class of flavonoids, is present in high concentrations in Alpina officinarum (common name: China or India root), which has been used as a spice and as a herbal medicine for a variety of ailments in Asia for centuries.…”

mentioning

confidence: 99%

The flavonoid galangin is an inhibitor of CYP1A1 activity and an agonist/antagonist of the aryl hydrocarbon receptor

1999

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SummaryThe effect of the dietary flavonoid galangin on the metabolism of 7,12-dimethylbenz [a]anthracene (DMBA), the activity of cytochrome P 450 1A1 (CYP1A1), and the expression of CYP1A1 in MCF-7 human breast carcinoma cells was investigated. Galangin inhibited the catabolic breakdown of DMBA, as measured by thin-layer chromatography, in a dose-dependent manner. Galangin also inhibited the formation of DMBA-DNA adducts, and prevented DMBA-induced inhibition of cell growth. Galangin caused a potent, dose-dependent inhibition of CYP1A1 activity, as measured by ethoxyresorufin-O-deethylase activity, in intact cells and in microsomes isolated from DMBAtreated cells. Analysis of the inhibition kinetics by double-reciprocal plot demonstrated that galangin inhibited CYP1A1 activity in a noncompetitive manner. Galangin caused an increase in the level of CYP1A1 mRNA, indicating that it may be an agonist of the aryl hydrocarbon receptor, but it inhibited the induction of CYP1A1 mRNA by DMBA or by 2,3,5,7-tetrachlorodibenzo-p-dioxin (TCDD). Galangin also inhibited the DMBA-or TCDD-induced transcription of a reporter vector containing the CYP1A1 promoter. Thus, galangin is a potent inhibitor of DMBA metabolism and an agonist/antagonist of the AhR, and may prove to be an effective chemopreventive agent.

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Comparative effects of flavonoids and model inducers on drug-metabolizing enzymes in rat liver

Cited by 107 publications

References 25 publications

Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity

Characterisation of metabolites of the putative cancer chemopreventive agent quercetin and their effect on cyclo-oxygenase activity

The Chemopreventive Effect of Taxifolin Is Exerted through ARE-Dependent Gene Regulation

The flavonoid galangin is an inhibitor of CYP1A1 activity and an agonist/antagonist of the aryl hydrocarbon receptor

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