Pathways of metabolism of [1'-14C]-trans-anethole in the rat and mouse.
This study describes the metabolic fate of trans-4'-methoxyprop-[1-14C]enylbenzene, the natural flavor compound trans-anethole, in rats and mice given single doses of 250 mg/kg body weight. In both rats and mice, an essentially quantitative (> 95% of dose) recovery of 14C was obtained with the majority in the 0-24 hr urine. Separation and identification of 18 urinary anethole metabolites were achieved by radio-HPLC, chemical derivatization, and GC/ MS. Anethole undergoes three primary oxidation pathways-O-demethylation, omega-side chain oxidation, and side chain epoxidation-followed by a variety of secondary pathways of oxidation and hydration, the products of which are extensively conjugated with sulfate, glucuronic acid, glycine, and glutathione. A novel major metabolite has been characterized in the rat, apparently originating from conjugation of the epoxide with glutathione, namely S-[1-(4'-methoxyphenyl)-2-hydroxypropane]-N-acetylcysteine. These metabolites are discussed in terms of the pathways responsible for and the toxicological consequences of their formation.
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Imperial College School of Medicine at St. Mary's, London, UK.
Caldwell
J
J
D000111:Acetylcysteine / Q000037:antagonists & inhibitors / Q000652:urine; D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000493:pharmacokinetics* / Q000652:urine; D001711:Biotransformation; D002250:Carbon Radioisotopes; D002851:Chromatography, High Pressure Liquid; D002934:Cinnamates / Q000652:urine; D005260:Female; D005421:Flavoring Agents / Q000493:pharmacokinetics*; D008401:Gas Chromatography-Mass Spectrometry; D005998:Glycine / Q000031:analogs & derivatives / Q000652:urine; D006626:Hippurates / Q000652:urine; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D002250:Carbon Radioisotopes; D002934:Cinnamates; D005421:Flavoring Agents; D006626:Hippurates; C104824:N-(4-methoxycinnamoyl)glycine; C104825:S-(1-(4'-methoxyphenyl)-2-hydroxypropyl)-N-acetylcysteine; C072836:4-methyoxybenzoyl-N-glycine; C006578:anethole; D005998:Glycine; D000111:Acetylcysteine