title: Formation of sulfur adducts of N-acetyl-p-benzoquinoneimine, an electrophilic metabolite of acetaminophen in vivo: participation of reactive persulfides.
abstract: While N-acetyl-p-benzoquinoneimine (NAPQI), an electrophilic metabolite of acetaminophen (APAP), has been found to undergo GSH conjugation associated with its detoxification, interaction of NAPQI with nucleophilic per- and polysulfides produced by cystathionine γ-lyase (CSE), cystathionine β-synthase, and/or other enzymes is not known. In the present study, we found that sulfur adducts such as the NAPQIH2-SSSCys adduct and the NAPQIH2-SSG adduct are produced in biological samples of mice upon APAP exposure. Our in vitro experiments indicated that the formation of these novel APAP metabolites is, at least in part, attributable to the interaction of CysSSnSH produced by CSE and GSH persulfide with APAP-derived NAPQI.
authors: Environmental Biology Section, Faculty of Medicine, University of Tsukuba , 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors: Yumi
authors: Y
authors: Abiko
authors: Department of Biochemistry, Keio University Graduate School of Pharmaceutical Sciences , Tokyo 105-8512, Japan.
authors: Isao
authors: I
authors: Ishii
authors: Department of Biochemistry, Keio University Graduate School of Pharmaceutical Sciences , Tokyo 105-8512, Japan.
authors: Shotaro
authors: S
authors: Kamata
authors: Laboratory of Pharmacology, Showa Pharmaceutical University , Tokyo 194-8543, Japan.
authors: Yukihiro
authors: Y
authors: Tsuchiya
authors: Laboratory of Pharmacology, Showa Pharmaceutical University , Tokyo 194-8543, Japan.
authors: Yasuo
authors: Y
authors: Watanabe
authors: Department of Biological Science, Graduate School of Science, Osaka Prefecture University , Osaka 599-8531, Japan.
authors: Hideshi
authors: H
authors: Ihara
authors: Department of Environmental Health Sciences and Molecular Toxicology, Tohoku University Graduate School of Medicine , Sendai 980-8575, Japan.
authors: Takaaki
authors: T
authors: Akaike
authors: Environmental Biology Section, Faculty of Medicine, University of Tsukuba , 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors: Yoshito
authors: Y
authors: Kumagai
mesh_terms: D000082:Acetaminophen / Q000737:chemistry*; D000818:Animals; D016227:Benzoquinones / Q000737:chemistry*; D002853:Chromatography, Liquid; D007097:Imines / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D013440:Sulfides / Q000737:chemistry*; D013455:Sulfur / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D016227:Benzoquinones; D007097:Imines; D013440:Sulfides; C051552:persulfides; D000082:Acetaminophen; D013455:Sulfur; C028473:N-acetyl-4-benzoquinoneimine