Function of multidrug resistance-associated protein 2 in acute hepatic failure rats

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• 作者：Tomoharu Yokooji ; Teruo Murakami ; Ryoko Yumoto ; Junya Nagai and Mikihisa Takano
• 关键词：Multidrug resistance-associated protein 2 ; 2 ; 4-Dinitrophenyl-S-glutathione ; CCl₄-induced acute hepatic failure ; Hyperbilirubinemia ; Intestinal efflux
• 刊名：European Journal of Pharmacology
• 出版年：2006
• 期刊代码：24_00142999
• 类别：neu
• 出版时间：28 September 2006
• 卷：546
• 期：1-3
• 页码：152-160
• 文件大小：350 K

摘要

The function of multidrug resistance-associated protein 2 (Mrp2) in the intestine and liver, as well as intestinal Mrp2 expression, was analyzed in CCl₄-induced acute hepatic failure rats with hyperbilirubinemia. The plasma level of bilirubin glucuronides, endogenous Mrp2-substrates, was 26 μM at 24 h after CCl₄ treatment. Mrp2 protein levels in jejunum decreased to 41%of control level. Mrp2-mediated efflux of 2,4-dinitrophenyl-S-glutathione (DNP-GSH), an Mrp2-substrate, in jejunum decreased to 31%of control in vitro, and was almost completely suppressed in vivo to the same level as that in the presence of probenecid, an Mrp2-inhibitor. Biliary excretion of DNP-GSH was suppressed to the same level as that inhibited by intravenous probenecid. The suppression of Mrp2 and the increased plasma bilirubin glucuronides recovered within 24 h thereafter. These results suggest that hyperbilirubinemia in disease states may be related to the systemic suppression of Mrp2 function.