Effect of tauroursodeoxycholic acid on bile flow and calcium excretion in ischemia-reperfusion injury of rat livers.
OBJECTIVE
Tauroursodeoxycholic acid is known to have a hepatoprotective action in cholestatic disorders. We evaluated whether oral pretreatment with tauroursodeoxycholic acid could protect the liver from ischemia-reperfusion injury, with particular regard to its effect on bile flow and biliary calcium excretion.


METHODS
A 1-hour in vivo ischemia-reperfusion model of 70% of the lobes of rat liver was used. Animals were divided into six groups (each group; n = 8); a non-ischemia sham group (CS), a control group without bile acids (CON), and 4 bile acid groups; 10 mg/kg and 50 mg/kg (U10, U50), taurocholic acid 10 mg/kg (CA10) and tauroursodeoxycholic acid 10 mg/kg (CD10). Bile acids were given orally for 7 days before operation.


RESULTS
Three hours after reperfusion, oral bile acid pretreatment failed to reduce the hepatic ischemia-reperfusion injury biochemically, but histological improvement was observed in the tauroursodeoxycholic acid groups. After reperfusion, tauroursodeoxycholic acid significantly increased bile flow from the ischemic liver, and also significantly increased serum calcium concentration. Although tauroursodeoxycholic acid did not change biliary calcium concentration, it significantly enhanced total biliary calcium output during reperfusion.


CONCLUSIONS
Thus, tauroursodeoxycholic acid inhibited tissue calcium accumulation and enhanced sinusoidal and biliary calcium output during hepatic ischemia-reperfusion. However, it is still unclear if calcium mobilization is part of the protective mechanisms of tauroursodeoxycholic acid in ischemia-reperfusion injury of the liver.
Ono
T
T
Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Nagasue
N
N
Kohno
H
H
Uchida
M
M
Takemoto
Y
Y
Dhar
D K
DK
Nakamura
T
T
D000704:Analysis of Variance; D000818:Animals; D001647:Bile Acids and Salts / Q000097:blood; D002118:Calcium / Q000097:blood*; D002779:Cholestasis / Q000188:drug therapy*; D005069:Evaluation Studies as Topic; D007536:Isomerism; D008099:Liver / Q000201:enzymology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013268:Stimulation, Chemical; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology*
D001647:Bile Acids and Salts; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; D002118:Calcium