摘要
Abstract
Objective To study and compare the effects of fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin and pazufloxacin) on the enzyme system of liver microsome cytochrome P4S0 in rat. Methods Thirty male Wistar rats were equally assigned into five groups: control group, levofloxacin (LV) group, gatifloxacin (GT) group, moxifloxacin (MX) group and pazufloxacin (PZ) group. Each drug was consecutively administered by tail vein injection for 7 days in a dosage of 120 mg/(kg·d). Liver microsomes were prepared by differential centrifugation, the concentration of protein in the liver microsome was measured by Lowry method, the content and activity of cytochrome P450 were detected by spectrophotometric determination, and the results were analyzed by one-way AN OVA. Results Compared with control group, the weight of liver in MX group and GT group was significantly reduced (P<0.01 or P<0.05); microsomal protein content of liver in LV group; GT group and MX group significantly increased (P<0.0l); the content of CYP450 in LV group and GT group increased (P<0.05 or P<0.0l); the content of cytochrome b5 (Cytb5) in GT group increased (P<0.05). Assessment of NADPH-CytC reductase activity in the liver microsomes showed that there was no statistically significant difference between drug groups and control group (P>(0.05). Assay of aminopyrine-N-demethylase activity showed that the difference in enzyme activity was statistically significant between the control group and groups LV, GT and MX (P<0.0l). Erythromycin-N-demethylase activity measurement revealed that the enzyme activity was lowered in GT group and slightly elevated in MX group, and the difference was statistically significant compared with that of control group (P<0.0l). Measurement of activity of rat liver microsomal CYP450 enzyme system subfamily showed that the BROD activity increased in LV, MX and PZ groups (P<0.0l), and slightly decreased in GT group as compared with control group (P<0.05). The PROD activity increased in GT group, but decreased in PZ group (P<0.0l). The EROD activity increased in all the four groups (P<0.0l). Conclusions The four fluoroquinolones have some effects on the enzyme system of liver microsome cytochrome P450 in rats, but the effects may be different (enhancement or attenuation of the enzymatic activity) depending on the enzymes, and the extent of the decrease of effect is in the following order: gatifloxacin, moxifloxacin, levofloxacin and pazufloxacin.关键词
氧氟沙星/细胞色素P450酶系统/微粒体,肝/代谢解毒,药物Key words
ofloxacin/ cytochrome P-450 enzyme system/ microsomes, liver/ metabolic detoxication, drug
分类
医药卫生
