Toxicology: Diazepam metabolism in the kidneys of male and female rats of various strains
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- KIM Hyung-Sub
- Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University
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- SAKAI Noriaki
- Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University
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- SAITO Konomu
- Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University
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- FUJITA Shoichi
- Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University
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- ISHIZUKA Mayumi
- Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University
書誌事項
- タイトル別名
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- Diazepam Metabolism in the Kidneys of Male and Female Rats of Various Strains
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抄録
Previously, we have reported drastic strain differences of diazepam metabolism in the livers of a variety of rat strain. In this study, to characterize strain and sex differences of diazepam metabolism in the kidney, renal microsomal diazepam metabolic activities were determined in the Dark Agouti (DA), Sprague-Dawley (SD), Brown Norway (BN) and Wistar (WS) strains of rat. We found that the major pathway of diazepam metabolism in the kidney was diazepam N-demethylation, which is different from that in the liver, 3-hydroxylation. A Dose-course (12.5-200 μM of diazepam) study revealed that the DA and WS male rats had higher diazepam N-demethylation activity than the SD and BN rats. In contrast to the males, a lower activity of diazepam N-demethylation was observed in female BN rats. By Western blot analysis, constitutive protein expressions of cytochrome P450 (CYP) 2C11, which is responsible for diazepam N-demethylation, were detected in the 4 strain in both the male and female rats, and the BN rats had lower expression levels of CYP2C11 protein. However, we did not observe significant differences in the kinetic parameters of diazepam N-demethylation. Our results suggested that there was a strain difference in CYP-dependent diazepam N-demethylation in the rat kidney, which is different from the finding in liver microsomes.<br>
収録刊行物
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- The Journal of Veterinary Medical Science
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The Journal of Veterinary Medical Science 72 (1), 7-11, 2010
公益社団法人 日本獣医学会
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詳細情報 詳細情報について
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- CRID
- 1390001206428124032
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- NII論文ID
- 130000134495
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- NII書誌ID
- AA10796138
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- ISSN
- 13477439
- 09167250
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- NDL書誌ID
- 10563471
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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