Sweeny D J, Reinke L A
Carcinogenesis. 1987 Jun;8(6):779-83. doi: 10.1093/carcin/8.6.779.
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.
在非循环灌注大鼠肝脏中研究了苯并[a]芘（BP）向酚类代谢物的代谢情况。输注BP（20微摩尔）30分钟后，形成的大多数酚类（78%）仍留在肝脏中。在灌注液和胆汁中检测到的酚类主要是葡糖醛酸（70%）和硫酸盐（20%）结合物。当灌注缓冲液中存在白蛋白时，酚类释放到灌注液中是肝脏消除的主要途径。在没有白蛋白的情况下，酚类的胆汁流出占主导。BP酚类葡糖醛酸和硫酸盐的胆汁浓度比其肝脏浓度至少高3.5倍，表明这些代谢物被主动转运到胆汁中。输注牛磺胆酸盐可提高BP酚类的胆汁消除速率，牛磺胆酸盐可将BP代谢物从细胞内储存部位置换出来。这些结果证实并扩展了先前的研究，这些研究表明，BP酚类从肝脏的释放是一个复杂的过程，受细胞内储存部位的可用性、胆汁排泄机制以及白蛋白等载体蛋白的存在影响。
