The Impact Of Fluoroquinolones On Hepatic Drug Metabolizing Enzymes, Gr And Gsh-px Activity In

Objective: To explore the effects of fluoroquinolones(FQs) on the content of cytochrome and the activities of aminopyrine N-demethylase(AMND),erythromycin N-demethylase(ERND),glutathione S-transferase(GST), gluathione reductase (GR)and gluathione peroxidase(GSH-PX) in the lung, brain, kidney, and small intestine of rats. Methods: ciprofloxacin, tosufloxacin and sparfloxacin were selected to represent FQs, while carboxymethylcellulose was used as the control. The experiment was divided into two parts, in vitro and in vivo, 8 and 32 wistar rats were used in the research, respectively; lung, brain, kidney and small intestine of rats were took out and made to S9 mix. In vitro test, the rats was killed directly without drug intervention, CPFX,TFLX,SPFX or carboxymethylcellulose were added in the reaction architecture of S9 mix, the concentration of drug in reaction architecture was 1mmol/L; in vivo test, 32 rats were divided into 4 groups, before killing, the rats of 4 groups were continuously perfused with 0.25% carboxy- methylcellulose and CPFX,TFLX ,SPFX (1mmol/kg.weight)respectively for 7 days and one time per day. In the end, the content of P-450 and the activity of above-mentioned enzyme in the S9 mix was assayed with spectrophotometer. Results: In vitro and in vivo, low level of P-450 was detected in lung and kidney tissue, but there is no significant difference between the drug groups and the control group. Activities of AMND and GST of brain were inhibited significantly by CPFX, TFLX and SPFX with contrast to carboxymethycellulose(P<0.05), but the difference between the drug groups and the control group in vitro are not consistent with the results of in vivo, and the decline of the activity of GST in 4 tissues were not on the same level. The activity of ERND in kidney and small intestine can be detected but very low, and no activity of ERND was determined in lung and brain; meanwhile, even though the activities of ERND,GR and GSH-PX were inhibited by FQs in all 4 tissues, but it did not have significant difference. Conclusions: FQS can inhibit the activities of AMND and GST to some extent in some extrahepatic tissues, and it`sinhibition to GST in different tissues is not consistent. Meanwhile , there is an inhibition trend of FQs on ERND, GR and GSH-PX activities.