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目的考察呋喃二烯(furanodiene,FDE)对肝脏微粒体主要的细胞色素P450(CYP)酶活性的影响。方法采用探针底物法,考察FDE在体外孵育体系中对大鼠和人肝微粒体CYP1A、CYP2A、CYP3A、CYP2C、CYP2D、CYP2E1的抑制作用,并计算相应的IC50值;采用微粒体体外“鸡尾酒”孵育法(cocktail法),考察大鼠经低、高剂量FDE(40 mg·kg?1和160 mg·kg?1)连续灌胃7 d,其肝微粒体主要CYP酶活性的变化。结果 FDE对大鼠肝微粒体CYP2D1和CYP2C6/7有较弱的抑制作用,其IC50分别为15.8和23.8μmol·L?1;对人肝微粒体CYP2C9也有较弱的抑制作用,IC50为26.1μmol·L?1。与对照组比较,大鼠灌胃40 mg·kg?1 FDE,肝微粒体主要CYP酶活性无显著变化;灌胃160 mg·kg?1后,肝微粒体CYP2E1活性为对照组的164%。结论 FDE对大鼠和人肝微粒体CYP主要亚型的抑制作用较弱;40 mg·kg?1 FDE对大鼠肝微粒体主要CYP酶未显示明显诱导作用,160 mg·kg?1 FDE对肝微粒体CYP2E1有一定的诱导作用。
Objective To investigate the effects of furanodiene (FDE) on the activities of major cytochrome P450 (CYP) enzymes in liver microsomes. Methods The probe substrate method was used to investigate the inhibitory effect of FDE on the CYP1A, CYP2A, CYP3A, CYP2C, CYP2D and CYP2E1 in rat and human liver microsomes in vitro and to calculate the corresponding IC50 values. “Cocktails” incubation method (cocktail method) to investigate the low, high-dose FDE (40 mg · kg -1 and 160 mg · kg -1) continuous gavage 7 d, the liver microsomal major CYP enzyme activity Variety. Results FDE had a weaker inhibitory effect on CYP2D1 and CYP2C6 / 7 in rat liver microsomes with IC50 of 15.8 and 23.8μmol·L -1, respectively. The inhibitory effect of FDE on human liver microsomal CYP2C9 was also weaker with IC50 of 26.1μmol · L? 1. Compared with the control group, there was no significant change in the main CYP enzyme activity of the liver microsomes after intragastric administration of 40 mg · kg -1 FDE. After the intragastric administration of 160 mg · kg -1, the CYP2E1 activity of the liver microsomes was 164% of the control group. Conclusions FDE has a weak inhibitory effect on major CYP isoforms in rat and human liver microsomes. FDE at 40 mg · kg -1 does not show significant induction of major CYP enzymes in rat liver microsomes. FDE at 160 mg · kg -1 Liver microsomal CYP2E1 have a certain induction.