Combined Effect Of Cholestyramine And UDCA On Cholestatic Acute Liver Injury In Dogs

Cholestyramine is an anion exchange resin that binds bile acids in the intestinal tract,and prevents enterohepatic circulation of bile acids.Therefore it can reduce the intrahepatic bile acid concentration.Ursodeoxycholic acid(UDCA)is a hydrophilic bile acids,it can change composition of bile acid pool,competitively inhibit the toxic effect of hydrophobic bile acids on liver cells and,promote the excretion of intrahepatic bile,by these mechanisms UDCA protect liver cells from necrosis and apoptosis.In order to study combined effect of cholestyramine and UDCA on dogs with cholestatic liver injury caused by benign bile duct stricture,we estimate the curative effect of combination therapy from the following aspects.Test ? Establishment of model for dog benign biliary strictureEighteen healthy adult dogs about 5 kg were selected and randomly divided into three groups of six,including normal control group(N group),sham operation group(S group),benign biliary stricture group(BBS group).We ligated the common bile ducts of dogs in BBS Group incompletely to establish models for benign biliary strictures,and just separated common bile duct of dogs in S group.N group received no manipulation.The results showed,differences between S group and N group in the clinical symptoms,serum levels of biochemical parameters and antioxidant indicators,antioxidant levels of liver were not significant(p>0.05).After operations,BBS group showed significant changes.The serum biochemical parameters ALT,AST,ALP,GGT,TB,DB,TBA,and serum levels of antioxidant indicators MDA,GST increased rapidly.The serum level of antioxidant indicators SOD,T-AOC decline rapidly.The trends of indicators were different,but the differences between BBS group and N group or S group,in all of these indicators,were significant(p<0.05).compared with N group and S group,levels of liver MDA of BBS group increased significantly,and level of liver SOD,T-AOC,GST declined significantly(p<0.05).Histopathologic examination found,extensive hepatocellar vacuolar degenerations deformation and cholestasis occured in BBS group.On day 14,dogs in BBS group accepted cholangiography,results showed there were bile duct stenosis,but did not form complete obstructions.There was no death in our study.In general,the method of common bile duct incomplaete ligation can model cholestasis and acute liver injury induced by benign biliary strictures in dogs.This method is simple to perform,with few complications and low mortality,so that it is easy to promote.Test ? Combined effect of cholestyramine and UDCA on cholestatic acute liver injury in dogsTwenty-four healthy adult dogs about 5 kg were selected and randomly divided into four groups of six,including control group,cholestyramine group(C group),ursodeoxycholic acid group(UDCA group),and combination therapy group(combined group).Four groups all accepted ligations of common bile duct by the same method recommoned in Test I.We did not give any treatment to control group after operation.C group was given cholestyramine 4g daily by oral route,UDCA group was given UDCA 15mg/kg daily by oral route,the combined group was given cholestyramine 4g daily and UDCA 15mg/kg daily at different times respectively.Before operations and on day 1,3,5,7,10,14 after operations,we monitor the serum levels of biochemical parameters markers and antioxidant indicators continously,and measure antioxidant levels of liver on day 14.The results showed,three therapies all released cholestatic liver injury to some extent.Serum ALT,AST,ALP,GGT,TB,DB,TBA levels of combined group in each period are lower then other groups.Serum and liver levels of MDA of combined group were the lowest in four groups,and levels of SOD and T-AOC were higher than other groups.Serum GST level of combined group was lower than other groups,while GST level in liver tissue of combined group was higher than other groups.Histopathologic examination found,the degrees of hypatocytes swell,degeneration and cholestasis appeared in combined group were mild than other groups.No dogs died during the test.In general,cholestyramine,UDCA and combined use of cholestyramine and UDCA all can alleviate cholestatic liver injury in BBS dogs to some extent.However,The combined group showed milder cholestasis and liver injury,and better antioxidant effect.Combined effects of two drugs is better than that alone.