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

The inducing effects of some flavonoids (flavone, flavanone, tangeretin and quercetin) and model substances have been studied in rats, and the activity and the expression of drug-metabolizing enzymes have been compared in rats. The addition of flavonoids to the diet (0.3% w/w) for 2 weeks did not ch...

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Bibliographic Details
Published in:Toxicology (Amsterdam) 1996-11, Vol.114 (1), p.19-27
Main Authors: Canivenc-Lavier, Marie-Chantal, Vernevaut, Marie-France, Totis, Muriel, Siess, Marie-Hélène, Magdalou, Jacques, Suschetet, Marc
Format: Article
Language:English
Subjects:
Analysis of Variance
Animals
Antineoplastic Agents - toxicity
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Chemical agents
Cytochrome P-450
Cytochrome P-450 CYP1A1 - biosynthesis
Cytochrome P-450 CYP2B1 - biosynthesis
Cytochrome P-450 Enzyme System - biosynthesis
Enzyme Induction - drug effects
Flavanones
Flavones
Flavonoids
Flavonoids - toxicity
Glucuronosyltransferase - biosynthesis
Glutathione Transferase - biosynthesis
Immunoblotting
Induction
Isoenzymes
Life Sciences
Male
Medical sciences
NADH Dehydrogenase - biosynthesis
Quercetin - toxicity
Rats
Rats, Sprague-Dawley
Structure-Activity Relationship
Transferases
Tumors
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Summary:The inducing effects of some flavonoids (flavone, flavanone, tangeretin and quercetin) and model substances have been studied in rats, and the activity and the expression of drug-metabolizing enzymes have been compared in rats. The addition of flavonoids to the diet (0.3% w/w) for 2 weeks did not change the liver cytochrome P450 content nor the activities of the NADPH-cytochrome P450 and NADH-cytochrome b 5 reductases, but it affected the activities of phase I and phase II enzymes. Flavone, and to a lesser extent tangeretin, increased the activities mediated by the P450 1A1,2 (EROD) and 2B1,2 (PROD) as well as the activities of p-nitrophenol UDP-glucuronyl transferase (UGT) and glutathione transferase (GST). Flavanone mainly enhanced PROD, UGT and GST, whereas quercetin did not modify any enzyme activities. None of the tested flavonoids modulated the activities catalyzed by P450 2E1, 3A and 4A. Immunoblotting studies showed that flavone and tangeretin increased the expression of cytochrome P450 1A and 2B forms, whereas flavanone only induced cytochrome P450 2B. Flavone and to a lesser extent flavanone, markedly increased the phenol-UGT protein level. Both flavone and flavanone also increased the androsterone- and testosterone-UGTs, whereas tangeretin and quercetin did not increase any UGT isoform. We concluded that the flavonoids tested specifically affected the expression of the drug-metabolizing isozymes in rat liver, their inducing properties were dependent on their chemical structures.
ISSN:0300-483X
1879-3185
DOI:10.1016/S0300-483X(96)03412-9