Comparison of Pathologic Features in Experimental Hyperphosphatasemic Conditions in Beagle Dogs Treated with α-Naphthylisothiocyanate and Phenobarbital
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概要
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The present study was designed to clarify the pathologic features of hyperphosphatasemic conditions in association with drug metabolizing enzyme (DME) induction and cholestatic condition in dogs. Two (2) model compounds were selected; α-naphthylisothiocyanate (ANIT) and phenobarbital (PB). Groups of beagle dogs were orally given ANIT at 30 mg/kg or PB at escalating dose of 20 to 60 mg/kg for 3 weeks and subjected to in-life and postmortem examinations. Determination of hepatic DME and alkaline phosphatase (ALP) activity in liver tissue fractions as well as isoenzyme analysis of serum ALP were performed. Differences between the ANIT and PB groups were: (1) the serum enzyme profile in the ANIT group was characterized by remarkably elevated activity in leakage enzymes (ALT and AST) and ALP accompanied by a remarkable increase in plasma total bilirubin concentration and remarkable inhibition of ICG clearance, (2) the only noticeable finding in the serum enzyme profile in the PB group was remarkable elevation of ALP activity, and (3) microsomal P-450 content decreased in the ANIT group and increased in the PB group. Activities of aminopyrine demethylase and aniline hydroxylase shifted together with the change in microsomal P-450 content in the PB group, and (4) degenerative changes in the biliary system and liver cells were characteristic in the ANIT group and hyperplasia of the smooth surfaced endoplasmic reticulum was prominent in the PB group. The reported hyperphosphatasemia recorded in the PB-treated dogs has to be dealt with separately from the toxicologically significant changes seen in ANIT-treated dogs, since the source of ALP differed between the two conditions.
- 日本毒性病理学会の論文
- 2002-03-25
著者
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YOSHIKAWA Takashi
Department of Aerospace Engineering, University of Tokyo
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Yamaguchi Yuko
Kannami Laboratory Bozo Research Center Inc.
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WATANABE Dai
Kannami Laboratory, Bozo Research Center Inc.
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HOSHIYA Toru
Kannami Laboratory, Bozo Research Center Inc.
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NAGASHIMA Yoshikazu
Kannami Laboratory, Bozo Research Center Inc.
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OKANIWA Azusa
Kannami Laboratory, Bozo Research Center Inc.
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ISHII Toshiya
Kannami Laboratory, Bozo Research Center Inc.
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MATSUOKA Tetsuya
Kannami Laboratory, Bozo Research Center Inc.
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SAITO Hitoshi
Kannami Laboratory, Bozo Research Center Inc.
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HATAYAMA Kazuhisa
Kannami Laboratory, Bozo Research Center Inc.
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HARAYAMA Kazuhisa
Kannami Lab.Bozo Research Center Inc.
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Hoshiya Toru
Kannami Laboratory Bozo Research Center Inc.
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Watanabe Dai
Kannami Laboratory Bozo Research Center Inc.
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Watanabe D
Systems Development Labora-tory Hitachi Ltd.
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Okaniwa Azusa
Kannami Laboratory Bozo Research Center Inc.
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Ishii Toshiya
Kannami Laboratory Bozo Research Center Inc.
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Matsuoka Tetsuya
Kannami Laboratory Bozo Research Center Inc.
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Harayama Kazuhisa
Kannami Laboratory Bozo Research Center Inc.
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Nagashima Yoshikazu
Kannami Laboratory Bozo Research Center Inc.
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Ishii Toshiya
Kannami Lab. Bozo Res. Center Inc.
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Saitoh Hitoshi
Kannami Laboratory Bozo Research Center Inc.
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Yoshikawa Takashi
Department Of Pathology School Of Veterinary Medicine And Animal Science Kitasato University
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Matsuoka Tetsuya
Kannami Lab. Bozo Res. Center Inc.
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