[Effects of 18 alpha-glycyrrhizic acid on rat liver cytochrome P450 isoenzymes and phase II transferase].
OBJECTIVE
To study the effect of 18 alpha-glycyrrhizic acid (18 alpha-GL) on hepatic microsomal drug metabolizing enzymes in rats.


METHODS
18 alpha-GL (12.5, 50.0 mg.kg-1.d-1) were given i.p. to male Wistar rats for 3, 6 or 12 consecutive days. The rats were sacrificed 24 h after the last dose and the liver microsomes were prepared for analysis of cytochrome P450 (CYP) isozymes and phase II transferase activites.


RESULTS
Aniline hydroxylase (CYP2E1) activities in the rats treated with 18 alpha-GL (12.5, 50.0 mg.kg-1) for 6 days decreased dose-dependently by up to 53.2%; For 3, 6 or 12 days 7-ethoxyresorufin O-deethylase (CYP1A1) activities in the rats of 50 mg.kg-1 dose group decreased time-dependently by 17.6%, 38.3% and 47.3%, respectively; Erythromycin N-demethylase (CYP3A) activities was significantly inhibited from 23.1% to 34.3%. UDP-glucuronosyltransferase activities toward 7-hydroxy-4-methylcoumarin significantly increased ranging from 19.3% to 29.9%. UDP-glucuronosyltransferase activities toward 4-phenylphenol in the rats treated with 18 alpha-GL (12.5, 50.0 mg.kg-1) for 6 days increased by 45.9% and 70.3%. Glutathione S-transferase (GST) activities in the rats treated with 18 alpha-GL (12.5, 50.0 mg.kg-1) for 6 days increased by 13.7% and 48.3% in dose-dependent manner.


CONCLUSIONS
18 alpha-GL inhibited rat liver microsomal cytochrome P450 while induced phase II transferase.
Yang
J
J
Department of Pharmacology, First Affiliated Hospital, Wuhan University Medical School, Wuhan 430071, China. yangjingliu@yahoo.com.cn
Peng
R X
RX
Kong
R
R
Yu
J P
JP
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D014453:Glucuronosyltransferase / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D019695:Glycyrrhizic Acid / Q000494:pharmacology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
D000972:Antineoplastic Agents, Phytogenic; D019695:Glycyrrhizic Acid; D003577:Cytochrome P-450 Enzyme System; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating; D014453:Glucuronosyltransferase; D005982:Glutathione Transferase