| OBJECTIVE: Study the auxiliary protective effects of Xinlilin tablets and mechanism on chemical liver injury and evaluate its toxicological safety.METHODS: According to the requirements of the Ministry of health "health food inspection and evaluation technical specification"(2003edition),alcoholic liver injury model and carbon tetrachloride liver injury model were used to study the protective effect and mechanism of Xinlilin tablets on chemical liver injury.In the function study,three dose groups which were 125,250 and 750mg/kg,respectively,which were equivalent to 5,10 and 30 times of the recommended amount of people were used.In the alcoholic liver injury model,malonaldehyde(MDA),glutathione(GSH)activities,triglyceride(TG)concent in liver tissue were measured by comment kit and liver tissue pathology was analyzed by HE staining.In CCl4 induced liver injury model,alanine transaminase(ALT),aspartate transaminase(AST),malonaldehyde(MDA)and glutathione(GSH),glutathione peroxidase(GSH-Px)level of serum or liver tissue were analyzed and liver pathological changes were recorded.Bax and Bcl-2protein expression were detected by the immunohistochemical and Western blot,and the apoptosis of hepatocytes was detected by DNA fragmentation.At the same time,the acute toxicity test,30 d feeding test were carried out.the maximum tolerated dose of rats and mouse,weight of rats,feed intake,blood routine,blood biochemical parameters were measured and the pathological changes of liver were observed.Ames test,mouse bone marrow micronucleus test,mouse sperm aberration test were used to evaluate genetic toxicological safetyRESULT: In alcoholic liver injury model,compared with the normal control group,In model control group,the content of GSH in liver tissue was decreased,TG content increased,the score of hepatic steatosis in mice was significantly increased(P < 0.05 or P < 0.01),which showed that the model of alcoholic liver injury was established.compared with the model group,the content of GSH was increased(P < 0.01).The middle dose group and high dose group of TG content were decreased(P< 0.05).liver steatosis scores were decreased(P < 0.05 or P < 0.01).In the carbon tetrachloride liver injury model,compared with the normal control group,in model control group,the level of ALT and AST in serum of mice were increased,MDA levels were increased,GSH content and GSH-Px content were decreased.Compared with the model group,the ALT and AST levels and MDA content were decreased(P < 0.05 or P <0.01),the high dose group of GSH-Px level,the middle dose group and high dose group of GSH content were increased(P < 0.05 or P < 0.01),histopathology showed that Xinlilin tablets have protective effects on liver injury induced by carbon tetrachloride.In the DNA fragment detection experiment,the DNA ladder was observed.In western blot and immunohistochemistry experiments,the protein expression of Bax was down regulated,and the protein expression of Bcl-2 was up-regulated.In acute toxicity test,mice and rats had no symptoms of poisoning and death,the maximum tolerated dose were more than 18g/kg BW,according to the acute toxicity grading criteria,acute toxicity level of Xinlilin tablets is non-toxic.In the 30 d feeding test,compared with the control group,the result of rat body weight,food intake,blood routine and blood biochemical parameters,organ weight and organ body ratio index were no significant difference(P>0.05).The appearance of liver,spleen,kidney,gonad and other organs of rats and the pathological changes in pathological sections were not found,the experimental results show that three of the dose groups showed no obvious toxicity associated with Xinlilin tablets.In the Ames test,each dose group of revertant colonies were not more than two times of the control group,and each dose group had no obvious dose-response relationship,the experimental results shows that Ames is negative.In the mouse bone marrow micronucleus test,compared with negative control group,each dose group of micronucleus rate were not statistically significant(P > 0.05),while the positive control group was significantly(P < 0.01),the results were negative.In mouse sperm abnormality test,Compared with the negative control group,each dose group of Sperm deformity rate was no significant difference(P > 0.05),while the positive control group of Sperm deformity rate is higher than the negative control group.there was significant difference(P < 0.05).the results of the mouse sperm abnormality test is negative.In summary,the results of genetic toxicity test were negative.CONCLUSION: Xinlilin tablets has auxiliary protective effect on chemical liver injury,the mechanism may be related to the inhibition of cell apoptosis or antioxidant properties.At the same time,there were no obvious toxicity in acute toxicity test,30 d feeding test and three genetic.According to the Ministry of health "health food inspection and evaluation technical specifications"(2003 Edition)shows that Xinlilin tablets is an effective and safety of health food that has no toxicity and has auxiliary protective effect on chemical liver injury. |
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