Effect of sodium tauroursodeoxycholate (UR-906) on liver dysfunction in bile duct-ligated rats.
We investigated the effect of sodium tauroursodeoxycholate (UR-906) on cholestasis in common bile duct-ligated rats in comparison with the effect of dehydrocholic acid. UR-906 (30-180 mumol/kg) and dehydrocholic acid (180 mumol/kg) were intravenously given once daily for consecutive 20 days in rats and the common bile duct was ligated for the last 10 days. On the next day after the last test drug administration, serum biochemical and plasma hemostatic variables were determined. UR-906 significantly ameliorated the elevation of serum cholesterol, phospholipid, bilirubin and bile acid concentrations in bile duct-ligated rats. UR-906 significantly suppressed the prolongation of plasma prothrombin time and activated partial thromboplastin time. Furthermore, UR-906 significantly suppressed the decreases in plasma coagulation factor II and X activities. However, dehydrocholic acid did not cause significant changes in any of the variables examined in this model. These results suggest that UR-906 has a beneficial effect against cholestasis induced by bile duct ligation in rats and that this drug may be useful in the treatment of clinical cholestatic disorders.
Ishizaki
K
K
Pharmacological Research Laboratory, Tokyo Tanabe Co. Ltd., Japan.
Kinbara
S
S
Miyazawa
N
N
Takeuchi
Y
Y
Hirabayashi
N
N
Kasai
H
H
Araki
T
T
D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood; D001652:Bile Ducts / Q000503:physiopathology / Q000601:surgery; D001663:Bilirubin / Q000097:blood; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D002779:Cholestasis / Q000188:drug therapy* / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood; D003685:Dehydrocholic Acid / Q000494:pharmacology*; D004195:Disease Models, Animal; D005170:Factor X / Q000032:analysis; D006487:Hemostasis / Q000187:drug effects; D008026:Ligation; D008297:Male; D010314:Partial Thromboplastin Time; D010743:Phospholipids / Q000097:blood; D011516:Prothrombin / Q000032:analysis; D011517:Prothrombin Time; D051381:Rats; D017208:Rats, Wistar; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D010743:Phospholipids; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D011516:Prothrombin; D005170:Factor X; D002784:Cholesterol; D003685:Dehydrocholic Acid; D001663:Bilirubin