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

Yumi Abiko, Isao Ishii, Shotaro Kamata, Yukihiro Tsuchiya, Yasuo Watanabe, Hideshi Ihara, Takaaki Akaike, Yoshito Kumagai

Research output: Contribution to journalArticle

10 Citations (Scopus)

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 NAPQIH<inf>2</inf>-SSSCys adduct and the NAPQIH<inf>2</inf>-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 CysSS<inf>n</inf>SH produced by CSE and GSH persulfide with APAP-derived NAPQI.

Original languageEnglish
Pages (from-to)1796-1802
Number of pages7
JournalChemical Research in Toxicology
Volume28
Issue number9
DOIs
Publication statusPublished - 2015 Aug 24

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Acetaminophen
Metabolites
Sulfur
Cystathionine
Lyases
Detoxification
N-acetyl-4-benzoquinoneimine
persulfides
Enzymes
Experiments

ASJC Scopus subject areas

  • Toxicology

Cite this

Formation of Sulfur Adducts of N-Acetyl-p-benzoquinoneimine, an Electrophilic Metabolite of Acetaminophen in Vivo : Participation of Reactive Persulfides. / Abiko, Yumi; Ishii, Isao; Kamata, Shotaro; Tsuchiya, Yukihiro; Watanabe, Yasuo; Ihara, Hideshi; Akaike, Takaaki; Kumagai, Yoshito.

In: Chemical Research in Toxicology, Vol. 28, No. 9, 24.08.2015, p. 1796-1802.

Research output: Contribution to journalArticle

Abiko, Yumi ; Ishii, Isao ; Kamata, Shotaro ; Tsuchiya, Yukihiro ; Watanabe, Yasuo ; Ihara, Hideshi ; Akaike, Takaaki ; Kumagai, Yoshito. / Formation of Sulfur Adducts of N-Acetyl-p-benzoquinoneimine, an Electrophilic Metabolite of Acetaminophen in Vivo : Participation of Reactive Persulfides. In: Chemical Research in Toxicology. 2015 ; Vol. 28, No. 9. pp. 1796-1802.
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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.",
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AU - Abiko, Yumi

AU - Ishii, Isao

AU - Kamata, Shotaro

AU - Tsuchiya, Yukihiro

AU - Watanabe, Yasuo

AU - Ihara, Hideshi

AU - Akaike, Takaaki

AU - Kumagai, Yoshito

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