Caffeic acid inhibits organic anion transporters OAT1 and OAT3 in rat kidney.

Drug Metabolism and Drug Interactions Pub Date : 2013-01-01 DOI:10.1515/dmdi-2013-0050

Yuichi Uwai, Tatsuya Kawasaki, Tomohiro Nabekura

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引用次数: 8

Abstract

Background: Some food components influence drug elimination. Previously, we found that caffeic acid, present in coffee, fruits, and vegetables, strongly inhibited human homologs of organic anion transporters (OATs) OAT1 and OAT3, which are responsible for renal tubular secretion of anionic drugs. In this study, we examined the effect of caffeic acid on drug transport by OAT1 and OAT3 in the rat kidney.

Methods: The inhibitory effect of caffeic acid on rat OAT1 and OAT3 was assessed by drug uptake experiment using Xenopus laevis oocytes. Urinary excretion of phenolsulfonphthalein (PSP), a diagnostic agent secreted by renal OATs, was examined in rats, and the influence of caffeic acid was evaluated.

Results: Expression of rat OAT1 (rOAT1) and rOAT3 stimulated uptake of their typical substrates, p-aminohippurate and estrone sulfate, respectively, into oocytes, and caffeic acid inhibited them dose dependently. After intravenous injection of PSP in rats, 42.7% of the dose was excreted into urine up to 60 min, and the simultaneous administration of caffeic acid reduced it to 32.0%.

Conclusions: These findings show that caffeic acid inhibits OAT1 and OAT3 in the rat kidney.

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咖啡酸抑制大鼠肾脏有机阴离子转运体OAT1和OAT3。

背景:一些食物成分影响药物消除。此前，我们发现咖啡、水果和蔬菜中存在的咖啡酸，强烈抑制人体有机阴离子转运蛋白(OATs)的同源物OAT1和OAT3，它们负责肾小管阴离子药物的分泌。本研究考察了咖啡酸对大鼠肾脏中OAT1和OAT3转运药物的影响。方法:采用非洲爪蟾卵母细胞给药实验，观察咖啡酸对大鼠OAT1和OAT3的抑制作用。研究了大鼠尿中由肾OATs分泌的诊断试剂苯酚磺酞(PSP)的排泄量，并评价了咖啡酸对其的影响。结果:大鼠OAT1 (rOAT1)和rOAT3的表达分别刺激其典型底物对氨基马嘌呤和硫酸雌酮进入卵母细胞，咖啡酸对它们的抑制作用呈剂量依赖性。在大鼠静脉注射PSP后，42.7%的剂量排泄到尿中长达60分钟，同时给药咖啡酸使其减少到32.0%。结论:咖啡酸能抑制大鼠肾脏中OAT1和OAT3的表达。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Drug Metabolism and Drug Interactions

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