RT Journal Article
SR Electronic
T1 METABOLISM OF MYOSMINE IN WISTAR RATS
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1648
OP 1656
DO 10.1124/dmd.104.003087
VO 33
IS 11
A1 Wolfgang Zwickenpflug
A1 Stefan Tyroller
A1 Elmar Richter
YR 2005
UL http://dmd.aspetjournals.org/content/33/11/1648.abstract
AB 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 μmol/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 μmol/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 μmol/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. The American Society for Pharmacology and Experimental Therapeutics