摘要
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ig 18α GL 12 5和 5 0mg·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P45 0 (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 5 3 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 2 9 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)
AIM To study the effect of 18α glycyrrhizic acid (18α GL) on hepatic microsomal drug metabolizing enzymes in rats. METHODS 18α GL (12 5, 50 0 mg·kg -1 ·d -1 ) were given ip 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 18α 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 18α 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 18α GL (12 5,50 0 mg·kg -1 ) for 6 days increased by 13 7% and 48 3% in dose dependent manner. CONCLUSION 18α GL inhibited rat liver microsomal cytochrome P450 while induced phase II transferase.
出处
《药学学报》
CAS
CSCD
北大核心
2001年第5期321-324,共4页
Acta Pharmaceutica Sinica
