Document Detail


Excretion of metabolites in urine and faeces from rats dosed with the heterocyclic amine, 2-amino-9H-pyrido[2,3-b]indole (AalphaC).
MedLine Citation:
PMID:  15110096     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
2-amino-9H-pyrido[2,3-b]indole (AalphaC) is a mutagenic and carcinogenic heterocyclic amine formed during ordinary cooking. In model systems AalphaC can be formed by pyrolysing either tryptophan or proteins of animal or vegetable origin. In the present study, the in vivo metabolism of AalphaC in rats was investigated. Rats were dosed with tritium labelled AalphaC. Urine and faeces were collected over three days. The metabolites of AalphaC were characterised by HPLC-MS and quantified by liquid scintillation counting. Conjugated metabolites were characterised by enzymatic hydrolyses with beta-Glucuronidase or arylsulfatase. The data showed that the metabolic pattern of AalphaC was similar in all rats. About 55% of the dose was excreted in urine and faeces during 72 h and the major amount of AalphaC metabolites (31%) was excreted during the first 24 h. In addition to a small amount of unmetabolised AalphaC seven conjugated metabolites were characterised. Three minor metabolites were characterised as AalphaC-N(2)-glucuronide and glucuronic acid conjugates of 3-OH-AalphaC and 6-OH-AalphaC. Four metabolites were all characterised as sulphuric acid conjugates and accounted for the largest amount of metabolites excreted in urine. The two major sulphuric acid conjugates were identified as AalphaC-3-O-sulfate and AalphaC-6-O-sulfate, while the minor sulphuric acid conjugates were proposed to be other O-sulfonated metabolites. In faeces only AalphaC was excreted and accounted for about 12% of dose during the first 24 hours. Any activated metabolites of AalphaC were not detected in rat urine or faeces. In future accumulation or binding of AalphaC to macromolecules such as DNA and proteins has to be studied.
Authors:
H Frederiksen; H Frandsen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association     Volume:  42     ISSN:  0278-6915     ISO Abbreviation:  Food Chem. Toxicol.     Publication Date:  2004 Jun 
Date Detail:
Created Date:  2004-04-27     Completed Date:  2004-06-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8207483     Medline TA:  Food Chem Toxicol     Country:  England    
Other Details:
Languages:  eng     Pagination:  879-85     Citation Subset:  IM    
Affiliation:
Institute of Food Safety and Nutrition, Danish Veterinary and Food Administration, Mørkhøj Bygade 19, DK 2860 Søborg, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Administration, Oral
Animals
Carbolines / administration & dosage,  metabolism*,  urine
Chromatography, High Pressure Liquid
Feces / chemistry
Male
Mass Spectrometry
Rats
Rats, Wistar
Tritium / diagnostic use
Chemical
Reg. No./Substance:
0/Carbolines; 10028-17-8/Tritium; 26148-68-5/2-amino-9H-pyrido(2,3-b)indole

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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