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IDENTIFICATION OF METABOLITES IN URINE AND FECES FROM RATS DOSED WITH THE HETEROCYCLIC AMINE, 2-AMINO-3-METHYL-9H-PYRIDO2,3-bINDOLE (MeAαC)

IDENTIFICATION OF METABOLITES IN URINE AND FECES FROM RATS DOSED WITH THE HETEROCYCLIC AMINE,... Abstract 2-Amino-3-methyl-9 H -pyrido2,3- b indole (MeAαC) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeAαC can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study, the in vivo metabolism of MeAαC in rats was investigated. Rats were dosed with tritium-labeled MeAαC, and urine and feces were collected over 3 days. The metabolites of MeAαC were identified by high performance liquid chromatography-mass spectrometry and quantified by liquid scintillation counting. Conjugated metabolites were characterized by enzymatic hydrolyzes with β-glucuronidase or arylsulfatase. The data showed that the metabolic pattern of MeAαC was similar in all rats. About 65% of the dose was excreted in urine and feces, and the major amount of MeAαC-metabolites was excreted during the first 24 h. Thirty-four percent of the dose was found in the rat urine samples collected to 24 h. In addition to unmetabolized MeAαC and two phase I metabolites, 6-OH-MeAαC and 7-OH-MeAαC, the following conjugated metabolites were identified: MeAαC- N 2 -glucuronide, AαC-3-CH 2 O-glucuronide, 3-carboxy-AαC and 3-carboxy-AαC-glucuronide, and sulfate and glucuronide conjugates of 6-OH-MeAαC and 7-OH-MeAαC. Also, a large amount of a rather unstable compound proposed to be of MeAαC-N1-glucuronide was found. About 21% of the dose was excreted in feces during the first 24 h, and MeAαC and 7-OH-MeAαC were the only compounds identified in feces. Any activated metabolites of MeAαC were not detected in rat urine or feces. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Drug Metabolism and Disposition Am. Soc for Pharma & Experimental Therapeutics

IDENTIFICATION OF METABOLITES IN URINE AND FECES FROM RATS DOSED WITH THE HETEROCYCLIC AMINE, 2-AMINO-3-METHYL-9H-PYRIDO2,3-bINDOLE (MeAαC)

Drug Metabolism and Disposition , Volume 32 (6): 661 – Jun 1, 2004

IDENTIFICATION OF METABOLITES IN URINE AND FECES FROM RATS DOSED WITH THE HETEROCYCLIC AMINE, 2-AMINO-3-METHYL-9H-PYRIDO2,3-bINDOLE (MeAαC)

Drug Metabolism and Disposition , Volume 32 (6): 661 – Jun 1, 2004

Abstract

Abstract 2-Amino-3-methyl-9 H -pyrido2,3- b indole (MeAαC) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeAαC can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study, the in vivo metabolism of MeAαC in rats was investigated. Rats were dosed with tritium-labeled MeAαC, and urine and feces were collected over 3 days. The metabolites of MeAαC were identified by high performance liquid chromatography-mass spectrometry and quantified by liquid scintillation counting. Conjugated metabolites were characterized by enzymatic hydrolyzes with β-glucuronidase or arylsulfatase. The data showed that the metabolic pattern of MeAαC was similar in all rats. About 65% of the dose was excreted in urine and feces, and the major amount of MeAαC-metabolites was excreted during the first 24 h. Thirty-four percent of the dose was found in the rat urine samples collected to 24 h. In addition to unmetabolized MeAαC and two phase I metabolites, 6-OH-MeAαC and 7-OH-MeAαC, the following conjugated metabolites were identified: MeAαC- N 2 -glucuronide, AαC-3-CH 2 O-glucuronide, 3-carboxy-AαC and 3-carboxy-AαC-glucuronide, and sulfate and glucuronide conjugates of 6-OH-MeAαC and 7-OH-MeAαC. Also, a large amount of a rather unstable compound proposed to be of MeAαC-N1-glucuronide was found. About 21% of the dose was excreted in feces during the first 24 h, and MeAαC and 7-OH-MeAαC were the only compounds identified in feces. Any activated metabolites of MeAαC were not detected in rat urine or feces.

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References (42)

Publisher
Am. Soc for Pharma & Experimental Therapeutics
Copyright
Copyright © Drug Metabolism and Disposition
ISSN
0090-9556
eISSN
1521-009X
DOI
10.1124/dmd.32.6.661
pmid
15155558
Publisher site
See Article on Publisher Site

Abstract

Abstract 2-Amino-3-methyl-9 H -pyrido2,3- b indole (MeAαC) is a proximate mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems, MeAαC can be formed by pyrolyses of either tryptophan or proteins of animal or vegetable origin. In the present study, the in vivo metabolism of MeAαC in rats was investigated. Rats were dosed with tritium-labeled MeAαC, and urine and feces were collected over 3 days. The metabolites of MeAαC were identified by high performance liquid chromatography-mass spectrometry and quantified by liquid scintillation counting. Conjugated metabolites were characterized by enzymatic hydrolyzes with β-glucuronidase or arylsulfatase. The data showed that the metabolic pattern of MeAαC was similar in all rats. About 65% of the dose was excreted in urine and feces, and the major amount of MeAαC-metabolites was excreted during the first 24 h. Thirty-four percent of the dose was found in the rat urine samples collected to 24 h. In addition to unmetabolized MeAαC and two phase I metabolites, 6-OH-MeAαC and 7-OH-MeAαC, the following conjugated metabolites were identified: MeAαC- N 2 -glucuronide, AαC-3-CH 2 O-glucuronide, 3-carboxy-AαC and 3-carboxy-AαC-glucuronide, and sulfate and glucuronide conjugates of 6-OH-MeAαC and 7-OH-MeAαC. Also, a large amount of a rather unstable compound proposed to be of MeAαC-N1-glucuronide was found. About 21% of the dose was excreted in feces during the first 24 h, and MeAαC and 7-OH-MeAαC were the only compounds identified in feces. Any activated metabolites of MeAαC were not detected in rat urine or feces.

Journal

Drug Metabolism and DispositionAm. Soc for Pharma & Experimental Therapeutics

Published: Jun 1, 2004

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