Document Detail


Metabolism of myosmine in Wistar rats.
MedLine Citation:
PMID:  16079272     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The alkaloid myosmine is present not only in tobacco products but also in various foods. Myosmine is easily nitrosated, yielding 4-hydroxy-1-(3-pyridyl)-1-butanone (HPB) and the esophageal tobacco carcinogen N'-nitrosonornicotine. Due to its widespread occurrence, investigations on the metabolism and activation of myosmine are needed for risk assessment. Therefore, the metabolism of myosmine has been studied in Wistar rats treated with single oral doses of [pyridine-5-3H]myosmine at 0.001, 0.005, 0.5, and 50 micromol/kg body weight. Oral administration was achieved by feeding a labeled apple bite. Radioactivity was completely recovered in urine and feces within 48 h. At the two lower doses, 0.001 and 0.005 micromol/kg, a higher percentage of the radioactivity was excreted in urine (86.2 +/- 4.9% and 88.9 +/- 1.7%) as compared with the higher doses, 0.5 and 50 micromol/kg, where only 77.8 +/- 7.3% and 75.4 +/- 6.6% of the dose was found in urine. Within 24 h, urinary excretion of radioactivity was nearly complete with less than 4% of the total urinary output appearing between 24 and 48 h. The two major metabolites accounting for >70% of total radioactivity in urine were identified as 3-pyridylacetic acid (20-26%) and 4-oxo-4-(3-pyridyl)butyric acid (keto acid, 50-63%) using UV-diode array detection and gas chromatography-mass spectrometry measurements. 3-Pyridylmethanol (3-5%), 3'-hydroxymyosmine (2%) and HPB (1-3%) were detected as minor metabolites. 3'-Hydroxymyosmine is exclusively formed from myosmine and therefore might be used as a urinary biomarker for myosmine exposure in the future.
Authors:
Wolfgang Zwickenpflug; Stefan Tyroller; Elmar Richter
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-08-03
Journal Detail:
Title:  Drug metabolism and disposition: the biological fate of chemicals     Volume:  33     ISSN:  0090-9556     ISO Abbreviation:  Drug Metab. Dispos.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-10-27     Completed Date:  2006-08-04     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9421550     Medline TA:  Drug Metab Dispos     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1648-56     Citation Subset:  IM    
Affiliation:
Walther Straub Institute of Pharmacology and Toxicology, Ludwig-Maximilians University, Goethestrasse 33, D-80336 Munich, Germany. wolfgang.zwickenpflug@lrz.uni-muenchen.de
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MeSH Terms
Descriptor/Qualifier:
Alkaloids / analysis,  metabolism*,  urine
Animals
Dose-Response Relationship, Drug
Feces / chemistry
Female
Keto Acids / metabolism,  urine
Male
Pyridines / metabolism,  urine
Rats
Rats, Wistar
Time Factors
Tobacco / chemistry
Chemical
Reg. No./Substance:
0/4-oxo-4-(3-pyridyl)butanoic acid; 0/Alkaloids; 0/Keto Acids; 0/Pyridines; 532-12-7/myosmine

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


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