Bile Acid-Induced Elevated Oxidative Stress in the Absence of Farnesoid X Receptor(Biochemistry)
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概要
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The major function of farnesoid X receptor (FXR) is to maintain bile acid and lipid homeostasis. Fxr-null mice, in which the levels of hepatic bile acid and lipid have been elevated, develop spontaneous liver tumors. We evaluated differences in hepatic bile acid and triglyceride concentrations, and in generation of oxidative stress between wild-type mice and Fxr-null mice. The hepatic levels of 8-hydroxy-2'-deoxyguanosine (8OHdG). thio-barbituric acid-reactive substance (TBARS) and hydroperoxides, oxidative stress-related genes, and nuclear factor (erythroid-2 like) factor 2 (Nrf2) protein in Fxr-null mice were significantly higher than those in wild-type mice. An increase in the hepatic bile acid concentration in Fxr-null mice fed a cholic acid (CA) diet resulted in an increase in the hepatic levels of hydroperoxides, TBARS and 8OHdG, whereas a decrease in the hepatic concentration in mice fed a diet containing ME3738 (22β-methoxyolean-12-ene-3β,24(4β)-diol) resulted in a decrease in these oxidative stress marker levels. A good correlation was observed between the hepatic bile acid concentrations and the hepatic oxidative stress marker levels, although there was no significant correlation between the hepatic triglyceride concentrations and oxidative stress. The results show that oxidative stress is spontaneously enhanced in Fxr-null mice, which may be attributable to a continuously high level of hepatic bile acids.
- 社団法人日本薬学会の論文
- 2009-02-01
著者
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GONZALEZ Frank
Laboratory of Metabolism, National Cancer Institute, National Institutes of Health
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Gonzalez Frank
東北大学 薬学研究科薬物動態学
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Gonzalez F
Laboratory Of Metabolism National Cancer Institute National Institutes Of Health
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Gonzalez Frank
東北大学 薬学研究科薬物動態学分野
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YOSHINARI Kouichi
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, To
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YAMAZOE Yasushi
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, To
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Yamazoe Y
Division Of Drug Metabolism And Molecular Toxicology Graduate School Of Pharmaceutical Sciences Toho
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Yamazoe Yasushi
Department Of Pharmacology School Of Medicine Keio University:department Of Analytical Biochemistry
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SHIBASAKI Shigeki
Applied Pharmacology Research Laboratories, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd.
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KUROSAWA Tohru
Applied Pharmacology Research Laboratories, Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd.
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Gonzalez F
National Cancer Inst. Md Usa
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Shimada Miki
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, To
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Miyata Masaaki
東北大学 薬学研究科薬物動態学
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Miyata Masaaki
Division Of Drug Metabolism And Molecular Toxicology Graduate School Of Pharmaceutical Sciences Toho
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Miyata Masaaki
Division Of Drug Metabolism & Molecular Toxicology Graduate School Of Pharmaceutical Sciences To
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Yamazoe Y
Division Of Drug Metabolism And Molecular Toxicology Graduate School Of Pharmaceutical Sciences Toho
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Shimada M
Division Of Drug Metabolism And Molecular Toxicology Graduate School Of Pharmaceutical Sciences Toho
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NOMOTO Masahiro
Division of Drug Metabolism and Molecular Toxicology, Graduate School of Pharmaceutical Sciences, To
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YIN Shanai
Applied Pharmacology Research Labs., Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd.
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KURATA Yasushi
Applied Pharmacology Research Labs., Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd.
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SUZUKI Kokichi
Applied Pharmacology Research Labs., Pharmaceutical Research Center, Meiji Seika Kaisha, Ltd.
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Yin Shanai
Applied Pharmacology Research Labs. Pharmaceutical Research Center Meiji Seika Kaisha Ltd.
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Suzuki Kokichi
Applied Pharmacology Research Labs. Pharmaceutical Research Center Meiji Seika Kaisha Ltd.
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Kurata Yasushi
Applied Pharmacology Research Labs. Pharmaceutical Research Center Meiji Seika Kaisha Ltd.
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Nomoto Masahiro
Division Of Drug Metabolism And Molecular Toxicology Graduate School Of Pharmaceutical Sciences Toho
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Miyata M
Graduate School Of Pharmaceutical Sciences Tohoku University
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Shimada Miki
Department Of Pharmacology School Of Medicine Keio University
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Yoshinari Kouichi
Division Of Drug Metabolism And Molecular Toxicology Graduate School Of Pharmaceutical Sciences Toho
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Yoshinari Kouichi
Div. Of Drug Metabolism And Molecular Toxicology Graduate School Of Pharmaceutical Sciences Tohoku U
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Gonzalez Frank
Laboratory Of Metabolism Division Of Basic Science National Cancer Institute
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Yamazoe Yasushi
Division Of Drug Metabolism & Molecular Toxicology Graduate School Of Pharmaceutical Sciences To
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Kurosawa Tohru
Applied Pharmacology Research Labs. Pharmaceutical Research Center Meiji Seika Kaisha Ltd.
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Yamazoe Yasushi
Division Of Drug Metabolism And Molecular Toxicology Graduate School Of Pharmaceutical Sciences Toho
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Shibasaki Shigeki
Applied Pharmacology Research Labs. Pharmaceutical Research Center Meiji Seika Kaisha Ltd.
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Yoshinari Kouichi
Division Of Drug Metabolism And Molecular Toxicology Faculty Of Pharmaceutical Sciences. Tohoku Univ
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Shimada Mitsuyo
Department Of Physiology Teikyo University School Of Medicine
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Shibasaki Shigeki
Applied Pharmacology Research Laboratories, Pharmaceutical Research Center, Meiji Seika Kaisha Ltd.
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Kurosawa Tohru
Applied Pharmacology Research Laboratories, Pharmaceutical Research Center, Meiji Seika Kaisha Ltd.
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Shimada Miki
Division of Drug Metabolism and Molecular Toxicology, Faculty of Pharmaceutical Sciences, Tohoku University
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