Effects of secretin on TCDCA- or TDCA-induced cholestatic liver injury in the rat.

Secretin, a gastrointestinal hormone, is known to act on bile duct epithelial cells and has been thought to have no effects on the bile acid transport in the liver. However, secretin was proved recently to stimulate biliary secretion of taurocholic acid (TCA) and elevate the maximum hepatic transport capacity of TCA. In this study, to evaluate the effect of secretin on the biliary secretion of taurochenodeoxycholic acid (TCDCA) or taurodeoxycholic acid (TDCA), which are known as cytotoxic bile acids, changes in bile flow, biliary excretions of bile acids and serum levels of TCDCA or TDCA were studied in a TCDCA- or TDCA-induced cholestatic rat model with and without secretin administration. Secretin prevented the decrease in bile flow and enhanced biliary excretions of bile acids and bicarbonate, but serum levels of TCDCA or TDCA at the end of the study showed no significant changes in the secretin group as compared with controls. Serum levels of alanine and asparate aminotransferases were highly elevated in all rats given TCDCA or TDCA. These data indicate secretin is a possible treatment for patients with prolonged intrahepatic cholestasis.