Gourley G R, Mogilevsky W, Arend R A, Siegel F L, Odell G B
Hepatology. 1985 Jul-Aug;5(4):610-4. doi: 10.1002/hep.1840050415.
Anesthesia-induced alterations in bilirubin conjugation were studied. Rats were fitted with bile duct and jugular vein catheters while anesthetized with diethyl ether, ketamine or pentobarbital. As anesthesia abated, bile was collected for the next 5 hr and analyzed for flow rate, total bilirubin excretion and bilirubin glucuronide composition. The high-performance liquid chromatography method used allowed direct analysis of bile without derivatization or extraction. Ether anesthesia was associated with a reversible suppression of diglucuronide formation and total bilirubin excretion, with reciprocal monoglucuronide changes. Bile flow and pigment excretion were variable with ketamine. Pentobarbital provided the most uniform excretion data, although the ratio of C-8:C-12 monoglucuronide varied with all drugs. These data are consistent with recently reported drug-induced alterations in hepatic uridine diphosphoglucuronic acid concentration and support the hypothesis that alterations in this substrate concentration are capable of influencing rates of hepatic glucuronide formation.
研究了麻醉诱导的胆红素结合变化。大鼠在使用乙醚、氯胺酮或戊巴比妥麻醉时,安装了胆管和颈静脉导管。随着麻醉消退,在接下来的5小时内收集胆汁,并分析其流速、总胆红素排泄量和胆红素葡萄糖醛酸苷组成。所采用的高效液相色谱法可直接分析胆汁,无需衍生化或萃取。乙醚麻醉与二葡萄糖醛酸苷形成和总胆红素排泄的可逆性抑制有关,同时伴有单葡萄糖醛酸苷的反向变化。氯胺酮使胆汁流量和色素排泄情况多变。戊巴比妥提供了最一致的排泄数据,尽管所有药物都会使C-8:C-12单葡萄糖醛酸苷的比例发生变化。这些数据与最近报道的药物诱导的肝尿苷二磷酸葡萄糖醛酸浓度变化一致,并支持这样的假设,即该底物浓度的变化能够影响肝葡萄糖醛酸苷的形成速率。