Effects of fenofibrate on plasma and hepatic transaminase activities and hepatic transaminase gene expression in rats
スポンサーリンク
概要
- 論文の詳細を見る
Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are widely used as sensitive markers of possible tissue damage, particularly liver toxicity. Lipid-lowering drugs, such as fibrates, slightly increase serum transaminase levels in humans, but there is little evidence that the phenomenon is related to drug-induced liver injury (DILI). Some in vitro studies have indicated that the elevations of serum transaminase activities after treatment of humans with fenofibrate, one of the fibrates, are related to increased transaminase synthesis in the hepatocytes rather than to transaminase leakage from the hepatocytes associated with cell lysis. In this study, male F344/DuCrlCrlj (Fischer) rats were treated once with fenofibrate at a dose level of 400mg/kg and the relationships between the pharmacological effects, blood and hepatic transaminase activities and the gene expression of the transaminases in the liver were investigated. Fenofibrate treatment slightly increased plasma transaminase activities in rats with the findings directly related to the pharmacological action of the drug. The increases were in parallel with increases in hepatic transaminase activities associated with increases in the transaminase genes in the liver and were not considered to be a consequence of hepatotoxicity from the drug. The modification in transaminase gene expression is likely to be secondary to the pharmacological action of fenofibrate. The evidence obtained in our study underlines the importance of gene regulation as a possible alternative mechanism for increased blood transaminase activities.
- 日本トキシコロジー学会の論文
- 2009-08-01
著者
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KOBAYASHI Akio
Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN TOBACCO INC.
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KUNO Hideyuki
Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN TOBACCO INC.
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SUGAI Shoichiro
Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN TOBACCO INC.
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SAKAKIBARA Hiroyuki
Graduate School of Nutritional and Environmental Sciences, University of Shizuoka
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SHIMOI Kayoko
Graduate School of Nutritional and Environmental Sciences, University of Shizuoka
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Shimoi Kayoko
Global Coe Program Univ. Of Shizuoka
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Kuno Hideyuki
Toxicology Research Lab. Central Pharmaceutical Research Institute Japan Tobacco Inc.
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Suzuki Yuusuke
Toxicology Research Laboratories Central Pharmaceutical Research Institute Japan Tobacco Inc.
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Sugai Shoichiro
Toxicology Research Laboratories Central Pharmaceutical Research Institute Japan Tobacco Inc.
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Sugai Shoichiro
Toxicology Research Lab. Central Pharmaceutical Research Institute Japan Tobacco Inc.
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Kobayashi Akio
Department Of Ophthalmology Omiya Medical Center Jichi Medical School
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Suzuki Yusuke
Toxicology Research Lab., Central Pharmaceutical Research Institute, JAPAN TOBACCO INC.
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Sakakibara Hiroyuki
Graduate School Of Nutritional And Environmental Sciences University Of Shizuoka
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Shimoi Kayoko
Graduate School Of Nutritional And Environmental Sciences And Global Coe Program University Of Shizu
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Kobayashi A
Toxicology Research Lab. Central Pharmaceutical Research Institute Japan Tobacco Inc.
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Sakakibara Hiroyuki
Inst. For Environmental Sciences Univ. Of Shizuoka
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Sakakibara Hiroyuki
Graduate School Of Nutritional And Environmental Sciences And Global Coe Program University Of Shizu
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Kobayashi Akio
Toxicology Res. Labs. Japan Tobacco Inc.
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Kakehashi Akihiro
Department Of Ophthalmology Omiya Medical Center Jichi Medical School
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Suzuki Yusuke
Toxicology Research Lab. Central Pharmaceutical Research Institute Japan Tobacco Inc.
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Koyanagi Akiharu
Graduate School Of Nutritional And Environmental Sciences Univ. Of Shizuoka
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SHIMOI Kayoko
Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka
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Shimoi Kayoko
Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
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