Effect of sodium tauroursodeoxycholate on phalloidin-induced cholestasis in rats.
We investigated the therapeutic effect of tauroursodeoxycholate on phalloidin-induced cholestasis in rats. Intrahepatic cholestasis was induced by administration of phalloidin (500 microg/kg, i.p.) for 7 days. From the day of the last phalloidin injection, tauroursodeoxycholate (60-360 micromol/kg) was given intravenously twice a day for 4 days. On the next day after the last tauroursodeoxycholate administration, bile flow, serum biochemical parameters and biliary lipid excretion rates were determined. Tauroursodeoxycholate significantly suppressed the decrease in bile flow and increases in serum alkaline phosphatase, leucine aminopeptidase and glutamic pyruvic transaminase activities, cholesterol, phospholipid and bile acid concentrations observed in phalloidin-induced cholestasis in rats. Furthermore, tauroursodeoxycholate significantly improved the biliary cholesterol and phospholipid excretion rates in phalloidin-induced cholestasis in rats. These results demonstrate the usefulness of tauroursodeoxycholate as a therapeutic agent in intrahepatic cholestasis.
Ishizaki
K
K
Pharmaceuticals Research Laboratory IV, Research Center, Mitsubishi-Tokyo Pharmaceuticals, Inc., 1000, Kamoshida-cho, Aoba, Kanagawa 227-0033, Yokohama, Japan. 4600370@mitsubishi-pharm.co.jp
Kinbara
S
S
Hirabayashi
N
N
Uchiyama
K
K
Maeda
M
M
D000410:Alanine Transaminase / Q000097:blood / Q000187:drug effects; D000469:Alkaline Phosphatase / Q000097:blood / Q000187:drug effects; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood / Q000187:drug effects; D001646:Bile / Q000187:drug effects / Q000378:metabolism; D001647:Bile Acids and Salts / Q000097:blood; D001659:Biliary Tract / Q000187:drug effects / Q000378:metabolism; D001663:Bilirubin / Q000097:blood; D002780:Cholestasis, Intrahepatic / Q000139:chemically induced / Q000188:drug therapy*; D002784:Cholesterol / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007931:Leucyl Aminopeptidase / Q000097:blood / Q000187:drug effects; D008297:Male; D010590:Phalloidine / Q000494:pharmacology*; D010743:Phospholipids / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
D001647:Bile Acids and Salts; D010743:Phospholipids; D010590:Phalloidine; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; D007931:Leucyl Aminopeptidase; D001663:Bilirubin