Compensatory Expression of MRP3 in the Livers of MRP2-Deficient EHBRs Is Promoted by DHA Intake
スポンサーリンク
概要
- 論文の詳細を見る
We have hypothesized a suppressive mechanism against dietary docosahexaenoic acid (22:6n-3; DHA)-induced tissue lipid peroxidation, in which the degradation products, including their conjugates, are excreted into the urine by xenobiotic or organic anion transporters. In this study, we employed parent-strain Sprague-Dawley rats (SDRs), together with their mutant strain, Eisai hyperbilirubinuria rats (EHBRs). EHBRs are deficient in multidrug resistance-associated protein (MRP) 2, and show defective urinary excretion of numerous xenobiotics and organic anions. Both strains of rats were fed a diet containing DHA at 8.4% of total energy for 31 d. In the livers of the DHA-fed rats, the level of free malondialdehyde (MDA) + 4-hydroxy-2-alkenals (HAE) fell, and conversely glutathione S-transferase (GST) activity increased in MRP2-deficient EHBRs as compared to the SDRs, suggesting that the glutathione (GSH)-conjugation reaction for the aldehydes generated on DHA intake was accelerated in the MRP2-deficient EHBRs. Since the gene expression of liver MRP3 in the MRP2-deficient EHBRs was amplified to compensate for DHA intake, it is thought that the transport of MRP3 substrates into the bloodstream, rather than MRP2-mediated excretion of its substrates into the bile, was promoted. Indeed, excretion of mercapturic acid (acetylcysteine conjugates derived metabolically from the conjugate of each aldehyde with GSH) into the urine increased significantly in MRP2-deficient EHBRs fed DHA.
- 社団法人 日本農芸化学会の論文
- 2009-11-23
著者
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SEKINE Seiji
Central Research Laboratory, The Nisshin OilliO Group
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Sekine Seiji
Central Research Laboratory The Nisshin Oillio Group
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SAITO Morio
Institute for Health Sciences, MIKI Corporation
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Sekine Seiji
Central Research Laboratory The Nisshin Oillio Group Ltd.
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Kubo Kazuhiro
Narabunka Women's College
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Saito Morio
Inst. For Health Sciences Miki Corp.
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Saito Morio
Institute For Health Sciences Miki Corporation
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Sekine Seiji
Central Research Laboratory of The Nisshin OilliO Group, LTD.
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- Compensatory Expression of MRP3 in the Livers of MRP2-Deficient EHBRs Is Promoted by DHA Intake
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