Metabolism of benzo[a]pyrene in the perfused rat liver: factors affecting the release of phenolic metabolites into the bile and perfusate.

Abstract

The metabolism of benzo[a]pyrene (BP) to phenolic metabolites was studied in the non-recirculating perfused rat liver. After 30 min of BP (20 microM) infusion most phenols formed (78%) remained in the liver. Phenols detected in the perfusate and bile were primarily glucuronide (70%) and sulfate (20%) conjugates. When albumin was present in the perfusion buffer, release of phenols into perfusate was the predominant route of elimination from the liver. In the absence of albumin, biliary efflux of phenols predominated. Biliary concentrations of BP phenolic glucuronides and sulfates were at least 3.5-fold higher than their hepatic concentrations, suggesting an active transport of these metabolites into bile. Rates of biliary elimination of BP phenols were enhanced by the infusion of taurocholate, which displaces BP metabolites from intracellular stores. These results confirm and extend previous studies which have demonstrated that the release of BP phenols from the liver is a complex process, influenced by the availability of intracellular storage sites, biliary excretion mechanisms and the presence of carrier proteins such as albumin.