Renal elimination of p-aminohippurate (PAH) in response to three days of biliary obstruction in the rat. The role of OAT1 and OAT3
Renal elimination of p-aminohippurate (PAH) in response to three days of biliary obstruction in the rat. The role of OAT1 and OAT3
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DOI：
10.1016/j.bbadis.2006.05.011
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发表时间：
2006-07-01
影响因子：
6.2
通讯作者：
Torres, Adriana Monica
中科院分区：
文献类型：
--
作者：
Brandoni, Anabel;Anzai, Naohiko;Torres, Adriana Monica
对机械性胆汁淤积受试者给予药物的药代动力学研究很少。本研究的目的是检查胆管结扎3天（血清胆汁酸和胆红素升高的峰值）对全身和全身的影响。大鼠模型中肾脏PAH清除率和皮质肾OAT 1和OAT 3表达的影响。PAH是肾脏有机阴离子转运系统的原型底物。雄性Wistar大鼠进行胆管结扎（BDL大鼠）。配对喂养的假手术大鼠作为对照。BDL大鼠显示出显著较低的全身PAH清除率。肾脏研究显示，BDL大鼠的肾脏清除率以及PAH的排泄和分泌负荷降低。BDL大鼠肾组织匀浆中OAT 1蛋白的表达没有改变，但在基底外侧膜中表达减少。相比之下，结扎后3天，肾皮质匀浆和基底外侧膜中的OAT 3丰度增加。免疫细胞化学研究（光镜和共聚焦免疫荧光显微镜分析）证实了这些转运蛋白的肾脏表达的变化。本研究证实了阻塞性胆汁淤积3天后OAT 1表达在PAH消除受损中的关键作用。(c)2006 Elsevier B.V.保留所有权利。
Pharmacokinetic studies of the drugs administered to subjects with mechanical cholestasis are scarce. The purpose of the present study was to examine the effects of bile duct ligation of 3 days (peak of elevation of serum bile acids and bilirubin) on the systemic and. renal PAH clearance and on the expression of cortical renal OAT1 and OAT3 in a rat model. PAH is the prototypical substrate of the renal organic anion transport system. Male Wistar rats underwent a bile duct ligation (BDL rats). Pair-fed sham-operated rats served as controls. BDL rats displayed a significantly lower systemic PAH clearance. Renal studies revealed a reduction in the renal clearance and in the excreted and secreted load of PAH in BDL rats. The OAT1 protein expression in kidney homogenates was not modified, but it decreased in the basolateral membranes from BDL rats. In contrast, OAT3 abundance in both kidney cortex homogenates and in basolateral membranes increased by 3 days after the ligation. Immunocytochemical studies (light microscopic and confocal immunofluorescence microscopic analyses) confirmed the changes in the renal expression of these transport proteins. The present study demonstrates the key role of OAT1 expression in the impaired elimination of PAH after 3 days of obstructive cholestasis. (c) 2006 Elsevier B.V. All rights reserved.