Content area
Full Text
Tauroursode oxycholic acid (TUDCA) is of potential benefit in chole static disorde rs. Howeve r, the effect of TUDCA on hepatic ischemia+ or - reperfusion injury is unknown. We studied this subje ct with particular regard to its role s in hepatic calcium mobilization. Thre e dose s of TUDCA were used with continuous intrave nous infusion (1.0, 0.1, and 0.01 m mol/kg body weight/min) . At 3 hr after 1 hr of ischemia and repe rfusion in 70% rat live r, high-dose TUDCA reduced hepatic repe rfused injury according to biochemical and histological findings and significantly increased bile flow afte r repe rfusion. It significantly incre ased tissue calcium content and serum calcium concentration afte r repe rfusion. Furthe rmore, it also enhanced biliary calcium concentration and total output during reperfusion. In conclusion, TUDCA has a salutary effect on ischemia+ or - repe rfusion injury of the live r. However, it is still uncle ar how the calcium mobilization induce d by TUDCA is associated with the hepatoprote ction against ischemia+ or - repe rfusion injury.
KEY WORDS: tauroursodeoxycholic acid; liver; ischemia+ or - repe rfusion; calcium.
It has been reported that ursodeoxycholic acid and its taurine conjugate s (TUDCA) clinically improve he patic structure and function in such chronic chole static live r diseases as primary biliary cirrhosis, primary scle rosing cholangiti s, and othe rs (1+ or - 3) . Furthermore, many reports have demonstrated that TUDCA is beneficial against such experimental he patic injurie s as hydrophobic bile acid-induce d cholestasis in in vivo and in vitro studie s (4 + or - 6) and othe r chole static disorde rs (7) . Howeve r, it remains unknown whether TUDCA is effective in ischemia+ or - reperfusion injury of the live r (8, 9) .
Hepatic ischemia+ or - repe rfusion injury is a crucial clinical problem in live r transplantation, hepatectomy with inflow block, and various types of shock. Bile production is an organ-spe cific function of the live r. Hepatic ischemia reduces and then promptly stops bile excre tion. After live r repe rfusion, bile production recurs gradually when the length of ischemia is limited. Prolonge d ischemia impairs bile secretion, resulting in hepatic failure and host...