Protective effects of ursodeoxycholic acid on chenodeoxycholic acid-induced liver injury in hamsters.
OBJECTIVE
To investigate the effects of ursodeoxycholic acid (UDCA) on chenodeoxycholic acid (CDCA)-induced liver injury in hamsters, and to elucidate a correlation between liver injury and bile acid profiles in the liver.


METHODS
Liver injury was induced in hamsters by administration of 0.5% (w/w) CDCA in their feed for 7 d. UDCA (50 mg/kg and 150 mg/kg) was administered for the last 3 d of the experiment.


RESULTS
At the end of the experiment, serum alanine aminotransferase (ALT) increased more than 10 times and the presence of liver injury was confirmed histologically. Marked increase in bile acids was observed in the liver. The amount of total bile acids increased approximately three-fold and was accompanied by the increase in hydrophobic bile acids, CDCA and lithocholic acid (LCA). UDCA (50 mg/kg and 150 mg/kg) improved liver histology, with a significant decrease (679.3 +/- 77.5 U/L vs 333.6 +/- 50.4 U/L and 254.3 +/- 35.5 U/L, respectively, P < 0.01) in serum ALT level. UDCA decreased the concentrations of the hydrophobic bile acids, and as a result, a decrease in the total bile acid level in the liver was achieved.


CONCLUSIONS
The results show that UDCA improves oral CDCA-induced liver damage in hamsters. The protective effects of UDCA appear to result from a decrease in the concentration of hydrophobic bile acids, CDCA and LCA, which accumulate and show the cytotoxicity in the liver.
Iwaki
Tomomichi
T
Research Laboratory III (Immunology), Pharmaceuticals Research Division, Mitsubishi Pharma Corporation, 1000 Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan. iwaki.tomomichi@mh.m-pharma.co.jp
Ishizaki
Kaoru
K
Kinoshita
Shuji
S
Tanaka
Hideki
H
Fukunari
Atsushi
A
Tsurufuji
Makoto
M
Imada
Teruaki
T
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury; D002635:Chenodeoxycholic Acid; D002756:Cholagogues and Choleretics / Q000494:pharmacology*; D006224:Cricetinae; D004435:Eating / Q000187:drug effects; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology / Q000517:prevention & control*; D008647:Mesocricetus; D014580:Ursodeoxycholic Acid / Q000494:pharmacology*
D001647:Bile Acids and Salts; D002756:Cholagogues and Choleretics; D002635:Chenodeoxycholic Acid; D014580:Ursodeoxycholic Acid; D000410:Alanine Transaminase