Ebselen, a glutathione peroxidase mimetic seleno-organic compound, as a multifunctional antioxidant. Implication for inflammation-associated carcinogenesis

Yoshimasa Nakamura, Qing Feng, Takeshi Kumagai, Koji Torikai, Hajime Ohigashi, Toshihiko Osawa, Noriko Noguchi, Etsuo Niki, Koji Uchida

Research output: Contribution to journalArticle

101 Citations (Scopus)

Abstract

Ebselen, a seleno-organic compound showing glutathione peroxidase-like activity, is one of the promising synthetic antioxidants. In the present study, we investigated the antioxidant activities of ebselen using a 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated mouse skin model. Double pretreatments of mouse skin with ebselen significantly inhibited TPA-induced formation of thiobarbituric acid-reacting substance, known as an overall oxidative damage biomarker, in mouse epidermis, suggesting that ebselen indeed acts as an antioxidant in mouse skin. The antioxidative effect of ebselen is attributed to its selective blockade of leukocyte infiltration and activation leading to attenuation of the H 2O 2 level. In in vitro studies, ebselen inhibited TPA-induced superoxide generation in differentiated HL-60 cells and lipopolysaccharide-induced cyclooxygenase-2 protein expression in RAW 264.7 cells. In addition, we demonstrated for the first time that ebselen potentiated phase II enzyme activities, including NAD(P)H:(quinone-acceptor) oxidoreductasel and glutathione S-transferase in cultured hepatocytes and in mouse skin. These results strongly suggest that ebselen, a multifunctional antioxidant, is a potential chemopreventive agent in inflammation-associated carcinogenesis.

Original languageEnglish
Pages (from-to)2687-2694
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number4
DOIs
Publication statusPublished - Jan 25 2002
Externally publishedYes

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Glutathione Peroxidase
Organic compounds
Carcinogenesis
Antioxidants
Inflammation
Skin
Tetradecanoylphorbol Acetate
Acetates
ebselen
HL-60 Cells
Enzyme activity
Biomarkers
Cyclooxygenase 2
Glutathione Transferase
Infiltration
Epidermis
Superoxides
NAD
Lipopolysaccharides
Hepatocytes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ebselen, a glutathione peroxidase mimetic seleno-organic compound, as a multifunctional antioxidant. Implication for inflammation-associated carcinogenesis. / Nakamura, Yoshimasa; Feng, Qing; Kumagai, Takeshi; Torikai, Koji; Ohigashi, Hajime; Osawa, Toshihiko; Noguchi, Noriko; Niki, Etsuo; Uchida, Koji.

In: Journal of Biological Chemistry, Vol. 277, No. 4, 25.01.2002, p. 2687-2694.

Research output: Contribution to journalArticle

Nakamura, Yoshimasa ; Feng, Qing ; Kumagai, Takeshi ; Torikai, Koji ; Ohigashi, Hajime ; Osawa, Toshihiko ; Noguchi, Noriko ; Niki, Etsuo ; Uchida, Koji. / Ebselen, a glutathione peroxidase mimetic seleno-organic compound, as a multifunctional antioxidant. Implication for inflammation-associated carcinogenesis. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 4. pp. 2687-2694.
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