Possible Mechanism of 2,3,4,7,8-Pentachlorodibenzofuran-induced Oxidative Stress : Enhanced Production of Hydrogen Peroxide and the Liver Injury

DOI HANDLE Web Site Open Access
  • Yamada Ken-ichi
    Graduate School of Pharmaceutical Sciences, Kyushu University
  • Takeda Tomoki
    Graduate School of Pharmaceutical Sciences, Kyushu University
  • Kuroki Hiroaki
    Daiichi Univerisity of Pharmacy
  • Mitoma Chikage
    Research and Clinical Center for Yusho Dioxin, Kyushu University Hospital
  • Uchi Hiroshi
    Department of Dermatology, Graduate School of Medical Sciences, Kyushu University
  • Furue Masutaka
    Research and Clinical Center for Yusho Dioxin, Kyushu University Hospital | Department of Dermatology, Graduate School of Medical Sciences, Kyushu University
  • Yamada Hideyuki
    Graduate School of Pharmaceutical Sciences, Kyushu Univerisity
  • Ishii Yuji
    Graduate School of Pharmaceutical Sciences, Kyushu Univerisity

Bibliographic Information

Other Title
  • 油症原因物質2,3,4,7,8-Pentachlorodibenzofuranによる酸化的ストレス惹起の推定機構 : 肝臓での過酸化水素産生亢進と肝障害
  • ユショウ ゲンイン ブッシツ 2,3,4,7,8-Pentachlorodibenzofuran ニ ヨル サンカテキ ストレス ジャッキ ノ スイテイ キコウ : カンゾウ デ ノ カサンカスイソ サンセイ コウシン ト カン ショウガイ

Search this article

Abstract

The mechanism of oxidative stress which is one of the major toxicities observed in 2,3,4,7,8-pentachlorodibenzofuran (PenCDF) -treated mice was studied. Previously, we evaluated the dose-response relationship on the wasting syndrome and oxidative stress elicited with PenCDF (0.3, 1.0, 5.0 and 10 mg/kg, once, p.o.). Of PenCDF doses examined, the wasting syndrome and oxidative stress were most marked in 5 mg/kg. In disagreement with this, the hepatic ethoxyresorufin-O-deethylase (EROD) activity which is a marker of aryl hydrocarbon receptor-dependent induction of cytochrome P450 1a1 (Cyp1a1) was most significantly elevated at 0.3 mg/kg. To clarify this discripancy, in this study, we determined the contents of Cyp1a1 and 1a2 protein. The content of Cyp1a1 was well correlated with the EROD activity up to the PenCDF dose 1.0 mg/kg while the induction profile of Cyp1a2 was not correlated with it. Although, at the PenCDF 5.0 mg/kg, the contents of Cyp1a1 and 1a2 protein were induced consistently, the EROD activity declined to the level far smaller than the PenCDF dose 1.0 mg/kg. Further, the NADPH consumption was comparable among the PenCDF dose examined. Instead, the hydrogen peroxide production was elevated in S9 fraction most markedly by PenCDF dose 5.0 mg/kg. In agreement with this, the marker of hepatic injury, the serumAST and ALT activities were also most elevated at the same dose. Therefore, it is possible that PenCDF elicits oxidative stress and hepatic injury through the production of hydrogen peroxide via the mechanism involving uncoupling of the P450s.

Journal

  • 福岡醫學雜誌

    福岡醫學雜誌 108 (3), 58-67, 2017-03-25

    Fukuoka Medical Association

Keywords

Details 詳細情報について

Report a problem

Back to top