INVESTIGATION OF PROTEOMIC BIOMARKERS IN IN VIVO HEPATOTOXICITY STUDY OF RAT LIVER : TOXICITY DIFFERENTIATION IN HEPATOTOXICANTS
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概要
- 論文の詳細を見る
We investigated the overall protein expression profiles in the in vivo hepatotoxicity of rats induced by four well-recognized hepatotoxicants. Acetaminophen (APAP), amiodarone (AMD), tetracycline (TC) and carbon tetrachloride (CTC) were administered to male rats by gavages and the liver at 24 hr post-dosing was applied to the proteomic experiment. Blood biochemistry and histopathology were examined to identify specific changes related to the compounds given. Protein expression in the liver was investigated by 2-dimensional gel electrophoresis (2DE), and spots showing a significantly different expression in treated versus control group were excised from gels and identified by Q-Tof mass spectrometer. They were well characterized based on their functions related to the mechanisms of toxicity of the compounds. Among them, we focused on the 8 proteins that were affected by all 4 compounds examined. Proteins related to oxidative stress response such as carbonic anhydrase III (CA3) and 60kDa heat shock protein (HSP60), and energy metabolism such as adenylate kinase 4 (AK4) were found. Moreover, hierarchical clustering analysis using 2D-gel spots information revealed the possibility to differentiate the groups based on their toxicity levels such as severity of liver damage. These results suggested that assessing the effects of hepatotoxicants on protein expression is worth trying to screen candidate compounds at the developmental stage of drugs.
- 日本トキシコロジー学会の論文
- 2006-02-24
著者
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HORII Ikuo
Worldwide Safety Sciences, Nagoya Laboratories, Pfizer Global Research and Development, Pfizer Japan
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Yamamoto Toshinori
Drug Safety Research & Development Pfizer Global Research & Development Nagoya Laboratories
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Yamamoto T
Showa Univ. Tokyo Jpn
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Yamamoto Toshinori
Department Of Biochemical Toxicology School Of Pharmaceutical Sciences Showa University
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Yamada Hiroshi
worldwide safety sciences
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Horii Ikuo
Showa Univ. (department Of Biochemical Toxicology School Of Pharmaceutical Sciences)
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Horii I
Drug Safety Research And Development Pfizer Global Research And Development Nagoya Laboratories. Pfi
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Horii Ikuo
Pfizer Global Research & Development Nagoya Laboratories Pfizer Inc.
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YAMAMOTO Toshinori
Worldwide Safety Sciences, Pfizer Global Research & Development, Nagoya Laboratories, Pfizer Inc.
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KIKKAWA Rie
Worldwide Safety Sciences, Pfizer Global Research & Development, Nagoya Laboratories, Pfizer Inc.
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Kikkawa Rie
Worldwide Safety Sciences Pfizer Global Research And Development Nagoya Laboratories Pfizer Inc.
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Kikkawa Rie
Worldwide Safety Sciences Global Research & Development Nagoya Laboratories Pfizer Inc.
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Yamada Hiroshi
Drug Safety Research & Development Pfizer Global Research & Development Nagoya Laboratories
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Kikkawa Rie
Pfizer Global Research & Development Toxicology Nagoya Laboratoreis
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Horii Ikuo
Worldwide Safety Sciences Pgrd Nagoya Laboratories Pfizer Inc.
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Yamamoto Toshinori
Departments Of Clinical Pharmacy And Pharmacognosy School Of Pharmaceutical Sciences Showa Universit
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Horii Ikuo
Worldwide Safety Sciences
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Horii Ikuo
Worldwide Safety Sciences Pfizer Global Research & Development Nagoya Laboratories Pfizer Inc.
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Horii Ikuo
Biochemical Toxicology School Of Pharmaceutical Sciences Showa University
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Yamada Hiroshi
Worldwide Safety Sciences Pfizer Global Research And Development Nagoya Laboratories Pfizer Japan In
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Yamamoto Toshinori
Department Of Pharmacology Medical College Of Oita
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