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Titolo:
IDENTIFICATION OF GOAT AND MOUSE URINARY METABOLITES OF THE PNEUMOTOXIN, 3-METHYLINDOLE
Autore:
SMITH DJ; SKILES GL; APPLETON ML; CARLSON JR; YOST GS;
Indirizzi:
WASHINGTON STATE UNIV,DEPT ANIM SCI PULLMAN WA 99164 WASHINGTON STATE UNIV,DEPT ANIM SCI PULLMAN WA 99164 UNIV UTAH,DEPT PHARMACOL & TOXICOL SALT LAKE CITY UT 84112
Titolo Testata:
Xenobiotica
fascicolo: 9, volume: 23, anno: 1993,
pagine: 1025 - 1044
SICI:
0049-8254(1993)23:9<1025:IOGAMU>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
INVITRO COVALENT BINDING; PULMONARY-EDEMA; GLUTATHIONE ADDUCT; ZEA-MAYS; SKATOLE; ACID; BIOACTIVATION; CONJUGATION; TISSUES; LIVER;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
D.J. Smith et al., "IDENTIFICATION OF GOAT AND MOUSE URINARY METABOLITES OF THE PNEUMOTOXIN, 3-METHYLINDOLE", Xenobiotica, 23(9), 1993, pp. 1025-1044

Abstract

1. Urine from goats dosed i.v. with 3-methylindole (3MI; 15 mg/kg) or[methyl-C-14] 3MI (15 mg/kg, 0.5 muCi/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-hydroxy-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 (400 mg/kg) or [ring-UL-C-14] 3MI (400 mg/kg, 125 muCi/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 metabolized 3MI to a mercapturate, 3-[(N-acetyl-L-cystein-S-yl)methyl]indole, which has been previously identified and was confirmed in this study. 6. 3-Methyloxindole was not identified in the urine of either goats or mice. 7. The major pathways of 3MI biotransformation in goats and mice is the formation of mono- and dihydroxy-3-methyloxindoles and their subsequent conjugation with glucuronic acid or sulfate. 8. There are no apparent qualitative differences in the biotransformation of 3MI between goats and mice that can account for their different sensitivities to 3MI-induced lunginjury.

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Documento generato il 26/01/20 alle ore 10:32:09