title: Metabolism of the carcinogen alpha-asarone in liver microsomes.
abstract: Alpha-asarone (1) is a naturally occurring phenylpropene found in several plants, e.g. Acorus calamus. 1-containing plant materials and essential oils thereof are used for flavoring foods and in many phytopharmaceuticals. 1 has been claimed to have positive pharmacological effects, however, it is carcinogenic in male mice (liver) and probably genotoxic. Since the metabolic pathways of 1 have not been investigated and its carcinogenic mode of action is unknown, we investigated the metabolism of 1 in liver microsomes of rat, bovine, porcine, and human origin using HPLC-DAD and LC-ESI-MS/MS and derived kinetic data on the metabolite formation. The main metabolic pathway was the side-chain hydroxylation leading to (E)-3'-hydroxyasarone (2). Epoxidation of 1 presumably led to (E)-asarone-1',2'-epoxide (4) which instantly hydrolyzed to form erythro- and threo-configured diols (5b+5a). As a minor reaction O-demethylation of 1 was observed. The metabolite formation showed little species-specific differences with the exception of porcine liver microsomes for which the formation of diols 5b+5a exceeded the formation of alcohol 2. The kinetic parameters imply a dependence of the pattern of metabolite formation from substrate concentration. On the basis of our results and earlier findings we hypothesize the genotoxic epoxide 4 being the ultimate carcinogen metabolically formed from 1.
authors.affiliation: University of Kaiserslautern, Food Chemistry and Toxicology, Erwin-Schroedinger-Strasse 52, 67663 Kaiserslautern, Germany.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Cartus
authors.affiliation: University of Kaiserslautern, Food Chemistry and Toxicology, Erwin-Schroedinger-Strasse 52, 67663 Kaiserslautern, Germany. Electronic address: schrenk@rhrk.uni-kl.de.
authors.forename: Dieter
authors.initials: D
authors.lastname: Schrenk
mesh_terms: D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000737:chemistry / Q000378:metabolism*; D002417:Cattle; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism*; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D013552:Swine
chemical_list: D000081248:Allylbenzene Derivatives; D000840:Anisoles; C012195:asarone
keywords: Alkenylbenzene; Asarone; Carcinogenicity; Liver microsomes; Metabolism; Phenylpropanoid