title: Chemical Interaction of Protein Cysteine Residues with Reactive Metabolites of Methyleugenol.
abstract: Methyleugenol (ME), an alkenylbenzene compound, is a natural ingredient of several herbs and is used as flavoring agent in foodstuffs and fragrance in cosmetics. The hepatotoxicity, cytotoxicity, and carcinogenesis of ME have been well documented, and metabolic activation has been suggested to involve in ME-induced toxicities. The objective of this study was to identify chemical identity of interactions of protein with reactive metabolites of ME. Modification of cysteine residues of protein was observed in microsomal incubations and mice after exposure to ME. Three types of protein modification derived from the corresponding epoxide, α,β-unsaturated aldehyde, and carbonium ion of ME were detected in vitro and in vivo. The protein adduction took place in time- and dose-dependent manners. Dexamethasone, ketoconazole, and l-buthionine sulfoximine increased the protein modification induced by ME, which was proportional to the hepatotoxicity of ME. The findings facilitate the understanding of mechanism action of ME toxicities.
authors.affiliation: Wuya College of Innovation, Shenyang Pharmaceutical University , Shenyang, Liaoning 110016, P. R. China.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Wuya College of Innovation, Shenyang Pharmaceutical University , Shenyang, Liaoning 110016, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Wuya College of Innovation, Shenyang Pharmaceutical University , Shenyang, Liaoning 110016, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Biochemistry, University of Washington , Seattle, Washington 98195, United States.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
authors.affiliation: Wuya College of Innovation, Shenyang Pharmaceutical University , Shenyang, Liaoning 110016, P. R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Wuya College of Innovation, Shenyang Pharmaceutical University , Shenyang, Liaoning 110016, P. R. China.
authors.forename: Jiang
authors.identifier: 0000-0002-0340-0275
authors.initials: J
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid; D003545:Cysteine / Q000737:chemistry*; D005054:Eugenol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D008099:Liver / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D011506:Proteins / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D011506:Proteins; C005223:methyleugenol; D005054:Eugenol; D003545:Cysteine