六味地黄丸对大鼠肝微粒体代谢酶P450活性的影响

目的:考察六味地黄丸对大鼠肝微粒体代谢酶P450活性的影响。方法:大鼠灌胃分别给予生理盐水、西咪替丁、苯巴比妥钠和六味地黄丸7d后,腹腔注射非那西丁,不同时间点采集血样,用HPLC法测定血浆中探针药物非那西丁的浓度,用DAS软件估算其药动学参数。结果:生理盐水组、西咪替丁组、苯巴比妥钠组和六味地黄丸组探针药物的t1/2分别为(93.5±9.2),(161.7±11.0),(85.4±9.0),(67.0±6.7)min。结论:六味地黄丸对大鼠肝微粒体代谢酶P450活性有一定的诱导作用。

漂白纸浆废水对鲫鱼(Carassius auratus)肝脏微粒体代谢酶的影响

实验研究了一种漂白纸浆废水对鲫鱼(Carassiusauratus)的急性毒性以及肝脏微粒体尿二磷酸葡萄糖醛酸转移酶(UDPGT)和谷胱甘肽硫转移酶(GST)的影响,在生物化学水平探索低浓度漂白纸浆水对鱼类的危害.实验结果表明,该漂白纸浆废水的96hLC50和168hLC50分别为43.90±3.09%和29.66±6.20%.暴露30d后,10%和12%原废水处理组能显著地诱导鲫鱼肝脏微粒体酶GST的活性,然而,8%、10%和12%原废水处理组能显著地抑制UDPGT的活性(P<0.05).

六味地黄丸对大鼠肝微粒体代谢酶P450活性影响的研究

目的:探讨六味地黄丸对大鼠肝微粒体代谢酶P450活性的影响。方法:分别采用生理盐水、六味地黄丸、西咪替丁和苯巴比妥钠给大鼠灌胃。连续7d后,腹腔注射非那西丁。采集不同时间点的血样,用HPLC法测定血浆中探针药物非那西丁的浓度,估算比较其探针药物的t1/2。结果:生理盐水组、西咪替丁组与六味地黄丸组比较,组间差异显著(P<0.01);苯巴比妥钠组与六味地黄丸组比较,组间差异不明显(P>0.05)。结论:大鼠肝微粒体代谢酶P450活性在六味地黄丸作用下会得到一定增强,但对大鼠的实验结果是否适用于人体,尚需进一步研究。

不同时辰鼠肝微粒体药物代谢酶的变化

本实验选择鼠类肝脏微粒体药物代谢酶活性变化指标,在不同时辰进行测定。结果表明:微粒体细胞色素 P450总量、NADPH-细胞色素 C 还原酶和二甲基亚硝胺脱甲基酶在雄性大鼠和两性小鼠均呈现明显昼夜节律性变化。其峰值在晚间亥时至子时,谷值在清晨寅时至卯时,日间波动在一定范围内,黄昏酉时明显上升,而后达到最高值。

Identification of the metabolite and cytochrome P450 isoforms involved in rat liver microsomal metabolism of TM208

To identify the metabolite and CYP450 isoforms involved in rat liver microsomal metabolism of TM208. The present study investigated the metabolism of TM208 and the effects of selective CYP450 inhibitors on the metabolism of TM208 in rat liver microsomes. Various specific inhibitors of CYP were used to identify the isoforms of CYP involved in the metabolism of TM208. The inhibitor of CYP2D and that of CYP2B had strong inhibitory effects on TM208 metabolism in a concentration-de- pendant manner, the inhibitor of CYP1A had a modest inhibitory effect, and the inhibitor of CYP3A seemed not to have an obvious inhibitory effect on TM208 metabolism. TM208 might mainly be metabolized by CYP2D and CYP2B in rat liver microsomes.

In vitro metabolism and inhibitory effects of atractylenolideⅡon various hepatic CYPs in HLMs

In the present study,we aimed to investigate the interaction between atractylenolideⅡ(AT-Ⅱ)and CYP450 enzyme in human liver microsomes,and to lay a theoretical foundation for predicting the possible interaction of AT-Ⅱin combination with drugs.The chemical inhibition experiment was carried out with specific inhibitors to clarify the CYP450 subtypes affecting the metabolism of AT-Ⅱ,and the mechanism,kinetics,and type of inhibition of CYP450 enzyme by AT-Ⅱwere studied by using the probe-based determination method of human liver microsome system with the related data of IC50 and Ki as evaluation indexes.The metabolism of AT-Ⅱwas affected by CYP1A2,CYP2C9 and CYP3A4 inhibitors,and the highest inhibition rates were41.35%,41.97%and 82.45%,respectively.The IC50 values of AT-Ⅱto five subtypes of P450 CYP2C9,CYP1A2,CYP2C19,CYP3A4 and CYP2D6 were 69.7,84.3,92.4,173.8 and 190.1μmol/L,respectively.The Ki values of AT-Ⅱto five subtypes of P450 CYP2C9,CYP1A2,CYP2C19,CYP3A4 and CYP2D6 were 190.6,179.1,>200,72.2 and 66.8,respectively.Among these enzymes,AT-Ⅱexhibited non-competitive inhibition on CYP1A2,showed competitive inhibition on CYP2C9 and CYP3A4,and displayed mixed AT-Ⅱinhibition on CYP2C19 and CYP2D6.CYP1A2,CYP2C9 and CYP3A4 were involved in the AT-Ⅱmetabolism,and AT-Ⅱexhibited different inhibitory mechanisms and strengths for the five subtypes of CYP450.