Takikawa H, Sano N, Ohki H, Yamanaka M
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Biochim Biophys Acta. 1989 Aug 8;1004(2):147-50. doi: 10.1016/0005-2760(89)90262-2.
Biliary excretion and biotransformation of tracer doses of [14C]lithocholic acid and its sulfate and glucuronide intravenously injected into bile-drainaged rats were compared. Biliary excretion efficiency was in the order of unconjugate sulfate glucuronide and all conjugates were completely excreted into bile within 60 min after injection. Only tracer doses of radioactivity were found in the liver and urine. About 90% of radiolabeled bile acids in bile were conjugated with taurine immediately after injection of lithocholic acid, whereas lithocholic acid-glucuronide was only partly conjugated with taurine all the time (less than 6%) and excreted into bile mainly as native compound. In the first 10 min, 66% of lithocholic acid-sulfate was conjugated with taurine and it gradually proceeded up to 87%. Hydroxylation at C-6 and C-7 positions of lithocholic acid proceeded time-dependently up to 45%. No hydroxylation was observed with lithocholic acid-sulfate or glucuronide. Differences of biliary excretion rate of these conjugates may be one of the reasons for the delayed decrease of sulfated and glucuronidated bile acids in serum after bile drainage to patients with obstructive jaundice of during the recovery of acute hepatitis than non-esterified bile acids.
比较了向胆管引流大鼠静脉注射示踪剂量的[14C]石胆酸及其硫酸盐和葡糖醛酸苷后的胆汁排泄和生物转化情况。胆汁排泄效率的顺序为未结合物＞硫酸盐＞葡糖醛酸苷，且所有结合物在注射后60分钟内均完全排泄到胆汁中。在肝脏和尿液中仅发现示踪剂量的放射性。注射石胆酸后，胆汁中约90%的放射性标记胆汁酸立即与牛磺酸结合，而石胆酸 - 葡糖醛酸苷始终仅部分与牛磺酸结合（不到6%），并主要以天然化合物形式排泄到胆汁中。在最初的10分钟内，66%的石胆酸 - 硫酸盐与牛磺酸结合，并逐渐上升至87%。石胆酸在C-6和C-7位的羟基化随时间进行，最高可达45%。石胆酸硫酸盐或葡糖醛酸苷未观察到羟基化。这些结合物胆汁排泄率的差异可能是梗阻性黄疸患者胆汁引流后或急性肝炎恢复期间血清中硫酸化和葡糖醛酸化胆汁酸比未酯化胆汁酸下降延迟的原因之一。
