Greater taurodeoxycholate biotransformation during backward perfusion of rat liver

Differing patterns of taurodeoxycholate (TDC) metabolism and biliary excretion were studied with a forward-and-backward perfusion model of the isolated rat liver. Livers were perfused with 8 microM TDC via either the portal vein (forward) or the hepatic vein (backward). Bile was collected, total bile acids measured enzymatically, and bile composition determined by high-pressure liquid chromatography and thin-layer chromatography. During backward perfusion 48% of infused TDC was metabolized to taurocholate (TC) and 22.0% to other minor TDC metabolites. During forward perfusion, however, only 16% of administered TDC was metabolized to TC and 6.5% to minor metabolites. Total bile acid output was similar for both forward and backward perfusions. The kinetics of biliary bile acid excretion also differed between forward and backward perfusion. The time necessary for 50% excretion of labeled TDC and its metabolites was 3.5 +/- 0.45 min during forward and 18 +/- 3.50 min during backward perfusion, a time difference of 14.5 min. The greater biotransformation of TDC during backward perfusion could be explained by its longer intracellular residence. The reason for the delayed excretion of TDC during backward perfusion is unknown.