加替沙星和环丙沙星对大鼠肝细胞色素P450酶系的影响

Effects of gatifloxacin and ciprofloxacin on hepatic cytochromes P450 in rats

目的 研究加替沙星和环丙沙星对大鼠肝微粒体细胞色素P450酶系的影响。方法 加替沙星和环丙沙星400 mg.kg-1灌胃给药大鼠,qd,7天后,用差速离心法制备大鼠肝微粒体,用Lowry法测定蛋白浓度,用分光光度计法检测6种肝微粒体细胞色素P450酶含量及活性,并用单因素方差分析进行统计。结果 加替沙星组的6种细胞色素P450酶的活性与空白对照组相比差异无统计学意义;而环丙沙星能抑制6种细胞色素P450酶中的b5、NADPH-CytC还原酶、氨基比林N-脱甲基酶、红霉素N-脱甲基酶和7-乙氧基香豆素脱烃酶的活性,对CYP450酶系有选择性抑制作用。结论 加替沙星对大鼠肝微粒体CYP450酶系无显著性影响,而环丙沙星对CYP450酶系有选择性抑制作用。

Objective To study the effects of gatifloxacin and ciprofloxacin on hepaticcytochromes P450. Methods After the mice were administered gatifloxacin andciprofloxacin once daily for 7 days,liver microsome were distilled by differentvelocity centrifugation. The Lowry method was used to measure the concentrationof protein in liver microsome. The activity of gatifloxacin on mice hepatic microsomalenzymes were study by spectrophotometer. Results Gatifloxacin did’t inhibitactivity of a number of hepatic enzymes (cytochrome b5, NADPH-cytochromecreductase, aminopyrine-N-demethylase, erythromycin-N-demethylase and coumarin7-hydroxylation), but ciprofloxacin inhibited these hepatic enzymes. ConclusionGatifloxacin has a low potential interaction with agents that are biotransformed bythese enzymes, but ciprofloxacin has a notable interaction with those agents.