The metabolism of [2-14C]indole in the rat

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Abstract
[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.