Dimethyl Diphenyl Bicarboxylate On Safety Testing And Effects On The Acute Liver Injury In Canine

DDB(Dimethyl Diphenyl Bicarboxylate)is a independently developed liver protective drugs of our country.It has significant effect of reducing transaminase,and has a good effect of protecting liver with clinical application for many years.But the research for DDB in the veterinary clinical medicine is still in the initial stage.There is few study of the effect of DDB for veterinary clinical liver disease.This research will from the following aspects to research clinical safety of DDB,and evaluate its protection of acute liver injury for dogs,and provide guidance for its clinical application.Test Ⅰ The establishment of the canine acute liver injury modelEighteen healthy adult dogs about 6 kg were used to establish dog acute liver injury model respectively with injection of carbon tetrachloride(CCl4)and acetaminophen(APAP).The methods as follows:blank group take as normal,CCl4 group subcutaneous inject 1 ml of 50%CCl4 per 1 kg,APAP group subcutaneous inject APAP solution(600 g·L-1,DMS solution)3 times according to dose and time as 0 h is 750 mg·kg-1,9 h and 24 h 200 mg·kg-1.Comparative the results of clinical physical signs and blood biochemical changes of the 3 group.Results:CCl4 group and APAP group successfully establishment the canine acute liver injury model.The two model groups were clinical signs depression,loss of appetite and the level of ALT,AST,TP,ALB,ALP are significant difference compared with the blank group(p<0.05).This indicates that carbon tetrachloride and acetaminophen can establish stable acute liver injury model.Test II Effects of DDB on the CCl4 acute liver injury in dogsEighteen healthy adult dogs about 6 kg were used to establish dog acute liver injury model of CCl4.Dogs was divided into three groups,each group were given with excipients,DDB and astragalus injection respectively.The serum level of ALT,AST,SOD,MDA and T-AOC were compared on the 0,1,2,3,5,7 day.Results:DDB and astragalus have very good protection effect for liver injury caused by carbon tetrachloride,They can reduce serum liver transaminase,and reduce the oxidative damage in dogs by CCl4 And contrast DDB and astragalus injection in the two groups of data,DDB is better than the astragalus injection.Test Ⅲ Effects of DDB on the APAP acute liver injury in dogsEighteen healthy adult dog about 6 kg were used to establish dog acute liver injury model of APAP.Dogs were divided into three groups,each group were given with excipients,DDB and astragalus injection respectively.The serum level of ALT,AST,SOD,MDA and GSH-PX were compared on the 0,1,2,3,5,7 day.Results:DDB and astragalus injection has certain protective effect for acetaminophen liver damage.For APAP cause liver damage,DDB in the aspect of reducing liver transaminase is stronger than astragalus injection(p<0.05).The DDB and astragalus injection have protective effects for oxidative damage caused by APAP.But there is no significant difference between DDB and astragalus injection.Test Ⅵ Clinical safety of DDB in dogsThe test was conducted to evaluate the clinical safety of DDB in dogs.Twenty four healthy adult dogs about 6 kg were selected and randomly divided into four groups.According to the recommended clinical dose(50 mg·kg-1)set 0 times,0 times,1 times,3 times,5 times the recommended clinical dose group.Administered once daily for consecutive 28 days.Dogs of the clinical signs and physical observation group test,compare groups of dogs in the experimental 0 day,7 days,14 days,21 days,28 days of hematology,blood biochemical index and the change of pathological histology of DDB the clinical safety of dogs.The results showed that the difference of each index difference between each dose group was not significant.