Effects of quinolones on liver microsome cytochrome p450 in rats / 解放军医学杂志

ABSTRACT

Objective To study and compare the effects of fluoroquinolones (levofloxacin, gatifloxacin, moxifloxacin and pazufloxacin) on the enzyme system of liver microsome cytochrome P450 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 ANOVA. Results Compared with control group, the weight of liver in MX group and GT group was significantly reduced (P0.05). 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<0.01). 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<0.01). Measurement of activity of rat liver microsomal CYP450 enzyme system subfamily showed that the BROD activity increased in LV, MX and PZ groups (P<0.01), 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<0.01). The EROD activity increased in all the four groups (P<0.01). 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.