Effect of liquorice and glycyrrhizin on rat liver carcinogen metabolizing enzymes.
We investigated the effect of single or repeated intake of conspicuous amounts of licorice root extract (LE, 3138 or 6276 mg/kg body weight (bw) per os) or its natural constituent glycyrrhizin (G, 240 or 480 mg/kg bw per os) on Sprague-Dawley rat liver monooxygenases. Whereas a single LE or G dose was unable to affect CYP superfamily, four daily doses induced CYP3A, CYP1A2 and to varying extents CYP2B1-linked monooxygenases. A boosting effect on testosterone 6beta- (CYP3A1/2, CYP1A1/2), 7alpha- (CYP1A1/2, CYP2A1), 16alpha- (CYP2B1, CYP2C11), 2alpha- (CYP2C11) and 2beta- (CYP3A1, CYP1A1) -dependent oxidases as well as on androst-4-ene-3,17-dione- (CYP3A1/2) -supported monooxygenases were also achieved. Harmful outcomes associated to CYP changes (e.g. cotoxicity, cocarcinogenicity and promotion) may be of concern.
Paolini
M
M
Department of Pharmacology, Biochemical Toxicology Unit, University of Bologna, Italy. paolini@biocfarm.unibo.it
Barillari
J
J
Broccoli
M
M
Pozzetti
L
L
Perocco
P
P
Cantelli-Forti
G
G
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D002273:Carcinogens / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D005260:Female; D006035:Glycyrrhiza; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D006900:Hydroxylation; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010936:Plant Extracts / Q000494:pharmacology*; D010946:Plants, Medicinal; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D002273:Carcinogens; D010936:Plant Extracts; D019695:Glycyrrhizic Acid; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C465138:Cyp3a23-3a1 protein, rat; D051544:Cytochrome P-450 CYP3A