18α-甘草酸二铵对大鼠肝脏细胞色素P450和II相酶的影响

目的研究18α-甘草酸二铵(18α-GL)对肝脏药物代谢酶的影响。方法♂Wistar大鼠ig18α-GL12.5和50mg·kg^-1,分别给药3，6和12d，对照组给等容量的溶媒。酶学测定肝微粒体细胞色素P450(CYP)，尿苷二磷酸葡萄糖醛酸转移酶(GT)和谷胱甘肽巯基转移酶(GST)活性。结果18α-GL抑制苯胺羟化酶,乙氧异唑脱乙基酶和红霉素脱甲基酶活性，抑制率分别可达53.2%，47.3%和34.3%；增加GT₁(底物为7-甲基-4-羟基-香豆素)，GT₂(底物为4-羟基联苯)和GST活性,分别可达29.9%，70.3%和48.3%。结论18α-GL对大鼠肝微粒体I相酶(CYP2E1,CYP1A1和CYP3A)主要是抑制作用，对II相酶(GT₁，GT₂和GST)是诱导。

Effects of 18 alpha-glycyrrhizic acid on rat liver cytochrome P450 isoenzymes and phase II transferase]

AIM: 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. CONCLUSION: 18 alpha-GL inhibited rat liver microsomal cytochrome P450 while induced phase II transferase.