Watkins J B, Siegers C P, Klaassen C D
Proc Soc Exp Biol Med. 1984 Oct;177(1):168-75. doi: 10.3181/00379727-177-41928.
The biliary and renal excretion of acetaminophen and its metabolites over 8 hr was determined in rats exposed to diethyl ether by inhalation for 1 hr. Additional rats were anesthetized with urethane (1 g/kg ip) while control animals were conscious throughout the experiment (surgery was performed under hexobarbital narcosis: 150 mg/kg ip; 30-min duration). The concentration of UDP-glucuronic acid was decreased 80% in livers from ether-anesthetized rats but was not reduced in urethane-treated animals when compared to that in control rats. The concentration of reduced glutathione was not affected by either urethane or diethyl ether. Basal bile flow was not altered by the anesthetic agents. Bile flow rate after acetaminophen injection (100 mg/kg iv) was increased slightly over basal levels for 2 hr in hexobarbital-treated control rats, was unaltered in urethane-anesthetized animals, and was decreased throughout the 8-hr experiment in rats exposed to diethyl ether for 1 hr. In control and urethane-anesthetized animals, approximately 30-35% of the total acetaminophen dose (100 mg/kg iv) was excreted into bile in 8 hr, while only 16% was excreted in rats anesthetized with diethyl ether. Urinary elimination (60-70% of the dose) was not altered by exposure to ether. Separation of metabolites by reverse-phase high-pressure liquid chromatography showed that ether decreased the biliary elimination of unchanged acetaminophen and its glucuronide, sulfate, and glutathione conjugates by 47, 40, 49, and 73%, respectively, as compared to control rats. Excretion of unchanged acetaminophen and the glutathione conjugate into bile was depressed in urethane-anesthetized animals by 45 and 66%, respectively, whereas elimination of the glucuronide and sulfate conjugates was increased by 27 and 50%, respectively. These results indicate that biliary excretion is influenced by the anesthetic agent and that diethyl ether depresses conjugation with sulfate and glutathione as well as glucuronic acid.
通过吸入乙醚1小时使大鼠暴露，测定了对乙酰氨基酚及其代谢产物在8小时内的胆汁和肾脏排泄情况。另外的大鼠用氨基甲酸乙酯（1 g/kg腹腔注射）麻醉，而对照动物在整个实验过程中保持清醒（手术在己巴比妥麻醉下进行：150 mg/kg腹腔注射；持续30分钟）。与对照大鼠相比，乙醚麻醉大鼠肝脏中UDP-葡萄糖醛酸的浓度降低了80%，但在氨基甲酸乙酯处理的动物中未降低。还原型谷胱甘肽的浓度不受氨基甲酸乙酯或乙醚的影响。基础胆汁流量未受麻醉剂改变。在己巴比妥处理的对照大鼠中，静脉注射对乙酰氨基酚（100 mg/kg）后2小时内胆汁流速比基础水平略有增加，在氨基甲酸乙酯麻醉的动物中未改变，而在暴露于乙醚1小时的大鼠中，在整个8小时实验过程中胆汁流速均降低。在对照和氨基甲酸乙酯麻醉的动物中，对乙酰氨基酚总剂量（100 mg/kg静脉注射）的约30 - 35%在8小时内排泄到胆汁中，而在乙醚麻醉的大鼠中仅排泄16%。暴露于乙醚对尿液排泄（剂量的60 - 70%）无影响。通过反相高压液相色谱法分离代谢产物表明，与对照大鼠相比，乙醚使未变化的对乙酰氨基酚及其葡萄糖醛酸、硫酸盐和谷胱甘肽结合物的胆汁排泄分别降低了47%、40%、49%和73%。在氨基甲酸乙酯麻醉的动物中，未变化的对乙酰氨基酚和谷胱甘肽结合物向胆汁中的排泄分别降低了45%和66%，而葡萄糖醛酸和硫酸盐结合物的排泄分别增加了27%和50%。这些结果表明胆汁排泄受麻醉剂影响，并且乙醚抑制了与硫酸盐、谷胱甘肽以及葡萄糖醛酸的结合。
