Formation of Sulfur Adducts of N-Acetyl-p-benzoquinoneimine, an Electrophilic Metabolite of Acetaminophen in Vivo: Participation of Reactive Persulfides

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• 作者：Yumi Abiko ; Isao Ishii ; Shotaro Kamata ; Yukihiro Tsuchiya ; Yasuo Watanabe ; Hideshi Ihara ; Takaaki Akaike ; Yoshito Kumagai
• 刊名：Chemical Research in Toxicology
• 出版年：2015
• 出版时间：September 21, 2015
• 年：2015
• 卷：28
• 期：9
• 页码：1796-1802
• 全文大小：478K
• ISSN：1520-5010

文摘

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 纬-lyase (CSE), cystathionine 尾-synthase, and/or other enzymes is not known. In the present study, we found that sulfur adducts such as the NAPQIH₂鈥揝SSCys adduct and the NAPQIH₂鈥揝SG 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 CysSS_nSH produced by CSE and GSH persulfide with APAP-derived NAPQI.