The Effect Of Drugs On The Liver Drug-metabolizing Enzymes In Alveolar Echinococcosis Mice

Objective:To study the effect of Echinococcus multilocularis(E. multilocularis) infection on the drug-metabolizing enzymes in the hosts’ liver and the regulation of pharmacological intervention to the drug-metabolizing enzymes of hepatic alveolar echinococcosis Balb/c mice.Methods:Microsomal and cytosolic fractions were isolated from livers of gerbils and Balb/c mice using the method of differential centrifugation and the protein concentration was measured by bicinchonininc acid(BCA) method. Then we measured the content of CYP450 and Cyt b5 with differential spectroscopy. The activities of 7-ethoxyresorufin-O-dealkylase(EROD) 、 7-methoxyresorufin-O-dealkylase(MROD) and 7-pentoxyresorufin(PROD)-O-dealkylase were measured by fluorescence spectrometer. The activities of NADPH-Cytochrome P450 reductase 、glutathione-S-transferases(GST) and flavine monooxygenases(FMO) were measured by UV-Visible spectrophotometer.Meanwhile,we measured the weight of alveolar hydatid cyst capsule rocks to evaluate the efficacy of albendazole and 3-bromopyruvate. Quantitive real-time PCR was used to measure the expression content of CYP1A1、CYP1A2、CYP2B10、CYP2E1、FMO1、FMO2、FMO3 and GST in the liver tissue of Balb/c mice.Results:1) Compared to non-infected group, the content of both CYP450 exhibited significantly lower in the infected gerbils and Balb/c mice(P < 0.05),while the content of Cyt b5 was lower in the infected gerbils(P < 0.05)and didn’t change in the infected Balb/c mice( P > 0.05). Among the five kinds of liver drug-metabolizing enzymes,the activitiy of CPR was increased and the activity of GST was significantly decreased(P < 0.05)in the infected gerbils and Balb/c mice.While those of EROD and MROD had no changes(P >0.05). The activity of FMO exhibited significantly higher in the infected gerbils(P < 0.05) and didn’t change in the infected Balb/c mice(P >0.05)2) After 6 weeks treatment, the efficacy of albendazole and 3-bromopyruvate were hoth good(P < 0.05)and there had no significantly difference between them(P >0.05). While when the time of therapy was as long as 10 weeks, the efficacy of albendazole was better than that of 3-bromopyruvate.3) Compared with the model group, the content of Cyt b5 exhibited significantly higher(P < 0.05)in the infected Balb/c mice after taking albendazole orally for 6 weeks. The activities of EROD、MROD and PROD markedly increased(P < 0.05), those of CPR and GST decreased(P < 0.05).While when the infected Balb/c mice taken 3-bromopyruvate orally for the same time, the content of Cyt b5 increased(P < 0.05). The activities of CPRand GST were decreased(P < 0.05),while those of EROD、MROD and PROD didn’t change(P >0.05).4) When the infected Balb/c mice taken albendazole orally for 6 weeks, the mRNA expression content of CYP1A1 and CYP1A2 exhibited significantly higher(P < 0.05), those of FMO3 and GST were decreased(P < 0.05), and others had no changes(P >0.05).While when the infected Balb/c mice taken 3-bromopyruvate orally for the same time, the mRNA expression content of FMO3 and GST dramaticly decreased(P < 0.05) and those of others didn’t change obviously(P >0.05).Conclusion:The infection of E. multilocularis can change the activities of the hosts, and the changes has racial difference. Moreover, albendazole and 3-bromopyruvate can change the mRNA expression content and the activities of drug-metabolizing enzymes subfamily in the infected Balb/c mice.