Effect Of Magnesium Isoglycyrrhizinate On Rat Liver Injury Induced By Isoniazid And Rifampicin And Expression Of CYP2E1 In Liver

Objective To establish the model of liver injury induced by isoniazid and rifampicin in rats and investigate the effects of magnesium isoglycyrrhizinate on the level of serum transaminase,bilirubin,liver tissues homogenate MDA,SOD,GSH-PX,liver morphology and the expression of CYP2E1in rats with liver injury induced by isoniazid and rifampicin.Methods One hundred male Wistar rats were randomly divided into normal control group(twenty),isoniazid+rifampicin group(HR group,seventy)and isoniazid group(H group,ten),treated with 0.9%sodium chloride 10ml/(kg·d),isoniazid 50mg/(kg·d)+rifampicin 50mg/(kg·d) and isoniazid 50mg/(kg·d) respectively by intragastric administration on an empty stomach.Rats of ten in normal control groups and eight in HR groups were randomly killed on day 14,and the rest of rats in HR groups were randomly divided into six groups with ten for each:HR model group(MC group),Gluthion group,stronger stronger neo-minophagen C group(SNMC group), magnesium isoglycyrrhizinate(MglG) in low,moderate and high dose group,the rats of which were treated with isoniazid and rifampicin intragastric administration, intraperitoneally injected with equal volume of 0.9%sodium chloride,reduced glutathione 250mg/(kg·d),stronger neo-minophagenC 16.7mg/(kg·d),magnesium isoglycyrrhizinate 15.6mg/(kg·d),31.2mg/(kg·d) and 62.4mg/(kg·d) respectively, simultaneously the rest of normal control group,H group were treated with equal volume of 0.9%sodium chloride and isoniazid intragastric administration with the dose mentioned above,and also intraperitoneally injected with equal volume of 0.9%sodium chloride for 14 days.All rats were killed on day 28.Histological analysis was carried out.The expression of CYP2E1 was detected by immunohistochemical method.Serum ALT,AST,TBIL,DBIL and liver tissues homogenate MDA,SOD,GSH—PX were measured.Results 1.Compared with normal control group,serum ALT,AST,TBIL,DBIL in HR groups were obviously evevated(P＜0.05),and hepatic histological activity index(HAI) in HR group increased(P＜0.05);serum ALT,AST in INH group were also obviously evevated(P＜0.05),but there was no significant difference in serum TBIL,DBILand hepatic HAI between two groups(P＞0.05).Compared with HR group of week 2,Serum TBIL,DBIL of HR group of week 4 declined,but there were no significant difference between two groups(P＞0.05) and there was no significant difference of hepatic HAI between two groups(P＞0.05).Compared with H group,Serum AST,TBIL,DBIL of HR group of week 4 were significantly evevated(P＜0.01),hepatic HAI in HR group of week 4 were significantly evevated(P＜0.05).2.Compare with normal control group,liver tissues homogenate MDA in HR group was significantly increased,simultaneously with decrease on liver tissues homogenates SOD,GSH—PX also(P＜0.05),and OD values of expression of CYP2E1 in HR group significantly increased(P＜0.05);liver tissues homogenate MDA in INH group was not significantly increased,simultaneously with decrease on liver tissues homogenates SOD,GSH—PX also(P＞0.05),but OD values of expression of CYP2E1 in INH group significantly increased(P＜0.05).There was no significant difference in liver tissues homogenate MDA,SOD,GSH—PX and OD values of expression of CYP2E1 between HR group of week 2 and that of week 4(P＞0.05).Compare with H group,liver tissues homogenate MDA in HR group of week 4 was significantly increased,simultaneously with decrease on liver tissues homogenates SOD,GSH—PX also(P＜0.05),and OD values of expression of CYP2E1 in HR group of week 4 were significantly evevated(P＜0.05). 3.Compared with MC group(I.e.HR group of week 4),serum ALT,AST in all therapy groups were obviously decreased(P＜0.05),but there was no significant decrease between serum TBIL,DBIL in MC group and that of therapy groups (P＞0.05),and hepatic HAI in all therapy groups obviously decreased(P＜0.05).Liver tissues homogenate MDA in all therapy group was significantly decreased,simultaneously with increase on liver tissues homogenates SOD,GSH—PX also(P＜0.05),and OD values of expression of CYP2E1 in all therapy groups significant decreased(P＜0.05).4.There was no significant difference in serum TBIL,DBIL,ALT,AST and liver HAl between MgIG groups and Gluthion or SNMC group(P＞0.05),and there was no significant difference in liver tissues homogenates SOD,GSH—PX and OD values of expression of CYP2E1 between MgIG groups and Gluthion or SNMC group(P＞0.05). There was no significant difference in Serum ALT,AST,TBIL,DBIL,hepatic HAI,liver tissues homogenate MDA,SOD,GSH—PX and OD values of expression of CYP2E1 between any two of different dosage groups of MgIG(P＞0.05).Conclusion 1.The hepatotoxicity induced by combination of isoniazid and rifampicin is more serious than that by isoniazid used alone,The hepatotoxicity induced by combination of the two drugs didn't aggravate with administration time prolonged.Liver injury mechanism induced by isoniazid and/or rifampicin may be related with the lipid peroxidation.2.Magnesium isoglycyrrhizinate have therapeutic effect on rats liver injury induced by isoniazid and rifampicin,which may be related with raise antioxidase activity,retarded oxidative stress and lipid peroxidation,down regulation expression of CYP2E1.3.There were no significant difference of effect on rat liver injury induced by isoniazid and rifampicin between MgIG and Gluthion,SNMC in short-term use.