Protective Effect of Zinc against Lipopolysaccharide/D-Galactosamine-Induced Lethality

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概要

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• Zinc is an essential and multifunctional element for all cells. Metallothionein (MT) is a low molecular weight, cystein-rich, metal-binding protein that is involved in zinc homeostasis. During the acute-phase reaction, hepatic MT production is induced and hepatic zinc accumulation is stimulated. We previously reported that MT-I and II-deficient (MT-null) mice are highly sensitive to the lethal effects of lipopolysaccharide (LPS) plus D-galactosamine (GalN). The sensitization may relate to attenuatoin of α_1-acid glycoprotein (AGP) expression in MT-null mice. In the present study, we hypothesized that MT-induced hepatic zinc accumulation promotes AGP expression and prevents LPS/GalN-induced lethality. To determine whether zinc reduces LPS/GalN toxicity, zinc was administered to mice. Simultaneous administration of zinc and LPS/GalN showed no effect on the lethality of LPS/GalN in mice. Zinc administration at 3 hr prior to LPS/GalN challenge reduced LPS/GalN-induced death. However, zinc pre-administration at 24 hr before LPS/GalN challenge did not reduce LPS/GalN-induced death. The expression of AGP mRNA was elevated at 3 hr after zinc administration, 24-hr pretreatment was ineffective. The protective effect of zinc was observed in both wild-type and MT-null mice. These results show that the protective effects of zinc were not caused by MT induction, but by AGP expression. We suggest that MT-induced hepatic zinc accumulation may promote AGP expression and thus prevent LPS/GalN-induced lethality.

• 公益社団法人日本薬学会の論文
• 2003-02-01

著者

• Itoh Norio

  Department of Toxicology and Safety Science, Graduate School of Pharmaceutical Sciences, Osaka Unive

• Kimura Tomoki

  Department of Toxicology, Faculty of Pharmaceutical Sciences, Setsunan University

• Nakanishi Tsuyoshi

  Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University

• Itoh N

  Department Of Toxicology Graduate School Of Pharmaceutical Sciences Osaka University

• ISOBE Masakazu

  Department of Toxicology, Faculty of Pharmaceutical Sciences, Setsunan University

• Tanaka K

  Institute Of Earth And Space Science Graduate School Of Science Osaka University

• 田中 宏治

  Med.safe.res.labs. Sankyo Co. Ltd. Of Shizuoka Pref.

• Tanaka K

  Department Of Toxicology Graduate School Of Pharmaceutical Sciences Osaka University:(present Office

• Isobe Masakazu

  Department Of Toxicology Faculty Of Pharmaceutical Sciences Setsunan University

• Itoh Norio

  Dep. Toxicol. Grad. School Pharmaceut. Sci. Osaka Univ.

• Tanaka Keiichi

  Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University

• Oguro Ikuyo

  Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University

• Takehara Miyako

  Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University

• Ishizaki Jun-ichi

  Department of Toxicology, Graduate School of Pharmaceutical Sciences, Osaka University

• Tanaka Katsushi

  Department Of Materials Science And Engineering Graduate School Of Engineering Kyoto University

• Tanaka Keiichi

  Department Of Toxicology Graduate School Of Pharmaceutical Sciences Osaka University:(present Office

• Tanaka Keiichi

  Dep. Toxicol. Grad. School Pharmaceut. Sci. Osaka Univ.

• Oguro Ikuyo

  Department Of Toxicology Graduate School Of Pharmaceutical Sciences Osaka University

• Takehara Miyako

  Department Of Toxicology Graduate School Of Pharmaceutical Sciences Osaka University

• Ishizaki Jun-ichi

  Department Of Toxicology Graduate School Of Pharmaceutical Sciences Osaka University

• Nakanishi T

  Sci. Univ. Tokyo Tokyo Jpn

• Nakanishi Tsuyoshi

  Department Of Toxicology Graduate School Of Pharmaceutical Sciences Osaka University:(present Office

• Nakanishi Tsuyoshi

  Department Of Biotechnology Graduate School Of Engineering Osaka University

• Tanaka K

  Kumamoto Univ. Kumamoto Jpn

• Kojitani Takatoshi

  Res. Inst. Of Pharmaceutical Sciences Musashino Univ.

• Kimura Tomoki

  Department Of Radiology Kagawa University

• Isobe Masakazu

  Dep. Of Toxicology Fac. Of Pharmaceutical Sciences Setsunan Univ.

• Tanaka K

  Kobe‐gakuin Univ. Kobe Jpn

• Tanaka Keiichi

  Department Of Emergency And Critical Care Medicine Fukuoka University Hospital

• Tanaka Keiichi

  Department Of Anatomy Tottori University School Of Medicine

• Kimura Tomoki

  Department Of Radiation Oncology Hiroshima University Graduate School Of Biomedical Sciences

• Itoh Norio

  Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University

• Nakanishi Tsuyoshi

  Department of Biochemistry, School of Medicine, Keio University

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