Biochemical and morphological parameters of taurolithocholate-induced cholestasis.

Abstract

Intravenous injection of sodium taurolithocholate (NaTL) into rats produces a dose-related cholestatic response. A dose of 100 mg/kg was chosen to study the temporal effects on bile flow, serum bilirubin (SB) concentrations, serum transaminase (SGPT) activity, and serum alkaline phosphatase (SAP) activity. Cessation of bile flow after NaTL injection or bile duct ligation (B.D.L.) was accompanied by progressive elevations of SB and SGPT; after NaTL, these parameters reached maximal values at a time when bile flow was returning to normal. Changes in SAP were similar in both NaTL-treated and B.D.L. groups. Elevation of SGPT and SB was also seen when a combination of NaTL and taurocholic acid (TC) was injected, although cholestasis was not produced. TC alone produced similar changes. NaTL injection produced changes in hepatic ultrastructure, of which the most marked were dilatation of biliary canaliculi and the endoplasmic reticulum. The disruption was marked at 12 h and was reversed at 24 h. This correlated with changes in SGPT and microsomal function as measured by zoxazolamine paralysis time. TC also produced elevation of SGPT in the isolated perfused rat liver. The above changes are consistent with obstruction of the biliary tract by NaTL precipitation. However, the data also indicate that a combination of NaTL and TC can elicit hepatocyte disturbances without causing a diminution in bile flow.