Study On Hepatotoxicity Reduction Mechanism Of Compound Tripterygium Wilfordii

Aim:To observe the effects of Compound Tripterygium Wilfordii (TW) on liver toxicity and its possible mechanismMethods:1. Rats were randomly divided into blank control group, positive control group, TW water extract low dose group, TW water extract high dose group.Blank control group were given the same volume of the solvent solution. All drugs were adiministered by intragastric administration (i.g.) for four weeks. After the last dose of the drugs, get blood in anesthetized rats, separate serum, detect the content of ALT,AST,TP,ALB,Glu and TGAfter killing the rats, we obtained pathological examination of liver with software. Another part of liver were prepared into10%liver homogenate,and the content of SOD,MDA,Cyt P450were detected either.2.Rats were randomly divided into blank control group, TW, Compound TW,TW+Rehmanniae Radix(RR),TW+Caulis Sinomenii(CS),TW+Stiff Silkworm(SS),TW+Panax Notoginseng(PN), Compound-RR, Compound-CS, Compound-SS, Compound-PN, Blank control group were given the same volume of the solvent solution. All drugs were adiministered by intragastric administration (i.g.) for four weeks. After the last dose of the drugs, get blood in anesthetized rats, separate serum, detect the content of ALT,AST,TP,ALB,Glu and TGAfter killing the rats, we obtained patholo-gical examination of liver with soft ware. Another part of liver were prepared into10%liver homogenate,and the content of SOD,MDA,and Cyt P450were detected either.3. Three dimen-sional culture system of hepatocyte were established,and the following research were did on the basis of this system:(1)MTT method was used to determine the effect of TW at different concentrations on the cell ability of hepatocyte for different time.The content of ALT,AST,LDH, SOD,MDA, GSH-Px and Cyt P450were detected.(2) Using different combinations of drugs(TW, Compound TW, TW+RR,TW+CS,TW+SS,TW+PN)in hepatocyte.MTT method was used to determine the effect of TW at different concentrations on the cell ability of hepatocyte for different time.The content of ALT,AST,LDH, SOD,MDA, GSH-Px and Cyt P450were detected.Results:1. After adiministering by intragastric administration (i.g.) for four weeks,comparing with blank control group,the drug group could rise the content of ALT,AST,LDH,MDAand reduce the content of TP,ALB,TBIL, SOD and CytP450. The changes in high dose group were more significantly (P<0.05,P<0.01).Histopathological observation showed that pathological changes were happened in the liver of the drug group.2. After adiministering by intragastric administration (i.g.) for four weeks,comparing with blank control group,the content of ALT,AST, LDH,MDA were rised and the content of TP,ALB,TBIL, SOD were reduced in the TW group. No significant change happened in the compound group.The using of RR and PN could improve the liver toxic caused by TW,but CS had the opposite effect.3. Three dimensional culture system of hepatocyte were used to reseach the cell toxicy caused by TW:TW could rise the content of ALT,AST,LDH,MDA and reduce the content of TP,ALB,TBIL, SOD and CytP450. Compatibility with RR/PN could reduce the content of ALT,AST,LDH,MDA,but compatibility with CS could rise them.Conelusion:Through comprehensively study on liver toxicity caused by TW in vivo and in vitro,it is revesled that the toxicity of TW may be affected by function of CytP450enzymes. Study of TW combination with different herbal in vitro and in vivo,the experimental results reveal that,the using of RR and PN could inprove liver toxic caused by TW,but CS made it more serious.So we speculate that in the compound TW,RR and PN reduced the liver toxic by affecting the CytP450enzymes.CS in the compound play synergistic rather than attenuated effect.