METABOLISM OF [2-14C]INDOLE IN RAT
METABOLISM OF [2-14C]INDOLE IN RAT
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DOI：
10.1042/bj0980266
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发表时间：
1966-01-01
影响因子：
4.1
通讯作者：
WILLIAMS, RT
中科院分区：
文献类型：
--
作者：
KING, LJ;PARKE, DV;WILLIAMS, RT
以[~（14）C]甲酸酯和邻甲苯胺为原料，经N-[~（14）C]-甲酰基甲苯胺合成了[2-~（14）C]吲哚。当给大鼠喂饲[14 C]吲哚（剂量70-80 mg/kg体重）时，排出速度相当快，在2天内，平均81%出现在尿液中，11%出现在粪便中，2.4%以二氧化碳的形式出现在呼出的空气中。放射性以硫酸吲哚酚（剂量的50%）、吲哚葡糖苷酸（11%）、羟吲哚（1.4%）、靛红（5. 8%）、5-羟基吲哚缀合物（3.1%）、N-甲酰基邻氨基苯甲酸（0. 5%）和未改变的吲哚（0.07%）。粪便中含有硫酸吲哚酚（0.4%剂量）和吲哚（0.2%），但尚未鉴别出主要代谢产物。用胆管插管喂养大鼠，平均5。6%剂量的[14 C]吲哚（20-60 mg/ kg体重）在2天内通过胆汁排出。放射性以硫酸吲哚酚（0. 8%剂量）和5-羟基吲哚缀合物（0. 6%）。大鼠将吲哚酚进一步代谢为N-甲酰邻氨基苯甲酸和邻氨基苯甲酸，并将羟吲哚代谢为5-羟基羟吲哚。与大鼠肝微粒体加上上清液在有氧条件下，吲哚给吲哚，羟吲哚，可能靛红，N-甲酰邻氨基苯甲酸和邻氨基苯甲酸，但在厌氧条件下只给羟吲哚。类似地，在有氧条件下，羟吲哚生成5-羟基羟吲哚、邻氨基苯甲酸和邻氨基苯乙酸。吲哚通过2条途径代谢，1条途径通过吲哚酚代谢为靛红、N-甲酰基邻氨基苯甲酸和邻氨基苯甲酸，另一条途径通过羟吲哚代谢为5-羟基羟吲哚，并可能代谢为邻氨基苯乙酸和邻氨基苯甲酸。本文报道了下列新化合物：4-羟基-2-硝基苯乙酸，3-、4-和5-苄氧基-2-硝基苯乙酸，5-和7-羟基吲哚和5-氨基吖啶吲哚硫酸酯。
[2-14C]Indole has been synthesized from [14c]formate and o-toluidine via N[14C]-formyltoluidine. When fed to rats, the 14c of [14C]indole (dose 70-80 mg/kg body wt.) is fairly rapidly excreted, and in 2 days an average of 81% appears in the urine, 11% in the feces and 2.4% as CO2 in the expired air. Radioactivity is excreted in the urine as indoxyl sulphate (50% of the dose), indoxyl glucuronide (11%), oxindole (1.4%), isatin (5. 8%), 5-hydroxyoxindole conjugates (3.1%), N-formylanthranilic acid (0. 5%) and unchanged indole (0.07%). The feces contain indoxyl sulphate (0.4% of the dose) and indole (0.2%), but the major metabolites have not been identified. Fed to rats with biliary cannulae an average of 5. 6% of a dose of[14C]indole (20-60 mg/ kg body wt.) is excreted in the bile in 2 days. Radioactivity is present as indoxyl sulphate (0. 8% dose) and 5-hydroxyoxlndole conjugates (0. 6%). Rats further metabolize indoxyl into N-formylanthranilic acid and anthranilic acid, and oxindole into 5-hydroxyoxindole. With rat-liver microsomes plus supernatant under aerobic conditions, indole gives indoxyl, oxindole, possibly isatin, N-formylanthranilic acid and anthranilic acid, but under anaerobic conditions gives only oxindole. Similarly, under aerobic conditions, oxindole gives 5-hydroxyoxindole, anthranilic acid and o-aminophenylacetic acid. Indole is metabolized by 2 pathways, 1 via indoxyl to isatin, N-formylanthranilic acid and anthranilic acid, and the other via oxindole to 5-hydroxyoxindole and possibly to o-aminophenylacetic and anthranilic acid. The following new compounds are described: 4-hydroxy-2-nitrophenylacetic acid, 3-, 4-, and 5-benzyloxy-2-nitrophenylacetic acid, 5- and 7-hydroxyox-indole and 5-aminoacridine indoxyl sulphate.