Identification of goat and mouse urinary metabolites of the pneumotoxin, 3-methylindole

1. Urine from goats dosed i.v. With 3-methylindole (3MI; 15 mg/kg) or [methyl-14C] 3MI (15 mg/kg, 0.5 μCi/kg) contained at least 11 metabolites of 3MI.2. Goat metabolized 3MI to sulfate conjugates of 4- or 7-hydroxy-3-methyloxindole, 5- or 6-hydroxy-3-methyloxindole, and 3,5- or 6-dihydroxy-3-methyloxindole; glucuronic acid conjugates of indole-3-carboxylic acid and 4- or 7-hydrexy-3-methyl-oxindole; and unconjugated 3-hydroxy-3-methyloxindole. Diastereoisomeric glucuronic acid conjugates of 3-hydroxy-3-methyloxindole were also identified in goat urine.3. Urine from mice dosed i.p. With 3MI (400mg/kg) or [ring-UL-14C] 3MI (400 mg/kg, 125 μCi/kg) contained at least six metabolites of 3MI.4. Mice metabolized 3MI to glucuronic acid conjugates of 3,5- or 6-dihydroxy-3-methyloxindole, 5- or 6-hydroxy-3-methyloxindole, and indole-3-carboxylic acid; and unconjugated indole-3-carboxylic acid. Unconjugated 3-hydroxy-3-methyloxindole was identified in mouse urine in a previous report.5. Both goats and mice metaboli...