GENE EXPRESSION PROFILE IN LIVER OF DIFFERING AGES OF RATS AFTER SINGLE ORAL ADMINISTRATION OF ACETAMINOPHEN
スポンサーリンク
概要
- 論文の詳細を見る
In order to verify the influence of the rat age on hepatotoxicity, male Sprague-Dawley rats of 6 (young) and 12 (adult) weeks of age were orally administered acetaminophen (APAP), isoniazid (INH), or carbon tetrachloride (CC14). Liver samples were obtained in a time-course manner, and changes in gene expression examined by an Affymetrix GeneChip. APAP caused more prominent hepatic injury with respect to pathology and blood biochemistry in adults than in young rats, whereas no obvious agerelated differences were observed in INH- or CC14-treated rats. Comparing gene expression in control rats, CYP3A13 was higher and GSTY2c was lower in adults, suggesting that production of the active metabolite of APAP is higher and its detoxification is lower in adults. The total amount of glutathione and total SH in rat liver was found to be higher in adult rats whereas the extent of its reduction by APAP was larger in adults. A detailed analysis of genes showing age-related differences revealed that some of them were different not in their extent but in their time course, i.e., the stress responses occurred earlier in the young than in the adult, resulting in a difference at 24 hr after dosing. These results suggest that the age-related difference in toxicity would be attributed to a higher expression of CYP3A1 3, producing the active metabolite of APAP as well as the lower expression of the detoxification enzyme, GSTY2c, in adult rats. Furthermore, these differences affect the time course of APAP toxicity. The present study clearly depicts the advantage of the multi-time, multi-dose protocol employed in our project for analyzing the mechanism of toxicity by gene expression pro filing.
- 日本トキシコロジー学会の論文
- 2006-12-15
著者
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Okuyama Manabu
国立医薬品食品衛生研究所
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Okuyama Manabu
Toxicogenomics Project National Institute Of Biomedical Innovation
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Okuyama Manabu
医薬基盤研究所 トキシコゲノミクスプロジェクト
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NAGAO Taku
National Institute of Health Sciences
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Nagao Taku
Food Safety Commission Of Japan
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Nagao Taku
Laboratory Of Pharmacology & Toxicology Graduate School Of Pharmaceutical Sciences The Universit
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Nagao Taku
Laboratory Of Pharmacology And Toxicology Graduate School Of Pharmaceutical Sciences The University
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Miwa Satoko
Exploratory Toxicology & Dmpk Research Laboratories Tanabe Seiyaku Co. Ltd.
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MORISHITA Katsumi
Toxicogenomics Project, National Institute of Biomedical Innovation
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MIZUKAWA Yumiko
Department of Pathophysiology, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liber
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KASAHARA Toshihiko
Toxicogenomics Project, National Institute of Biomedical Innovation
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TAKASHIMA Kayoko
Toxicogenomics Project, National Institute of Biomedical Innovation
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TORITSUKA Naoki
Toxicogenomics Project, National Institute of Biomedical Innovation
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MIYAGISHIMA Toshikazu
Toxicogenomics Project, National Institute of Biomedical Innovation
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URUSHIDANI Tetsuro
Toxicogenomics Project, National Institute of Biomedical Innovation
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Urushidani Tetsuro
Toxicogenomics Project National Institute Of Biomedical Innovation:department Of Pathophysiology Dos
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Urushidani Tetsuro
Laboratory Of Pharmacology & Toxicology Graduate School Of Pharmaceutical Sciences The Universit
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Miyagishima Toshikazu
Toxicogenomics Project National Institute Of Biomedical Innovation
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Torituka Naoki
Toxicogenomics Project National Institute Of Biomedical Innovation
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Toritsuka Naoki
Drug Safety Research Labolatories Eisai Co. Ltd.
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Kasahara Toshihiko
Toxicogenomics Project National Institute Of Biomedical Innovation
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Toritsuka Naoki
Toxicogenomics Project National Institute Of Biomedical Innovation
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Mizukawa Yumiko
Toxicogenomics Project National Institute Of Biomedical Innovation:department Of Pathophysiology Fac
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Takashima Kayoko
Toxicogenomics Project National Institute Of Health Sciences
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Nagao Taku
National Institute Of Health Sci.
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Takashima Kayoko
Toxicogenomics Project National Institute Of Biomedical Innovation
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Morishita Katsumi
Toxicogenomics Project National Institute Of Biomedical Innovation
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Urushidani Tetsuro
Toxicogenomics Project National Institute Of Biomedical Innovation
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