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Licensed Unlicensed Requires Authentication Published by De Gruyter October 29, 2013

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

  • Yuichi Uwai EMAIL logo , Tatsuya Kawasaki and Tomohiro Nabekura

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.


Corresponding author: Yuichi Uwai, PhD, Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, 1-100, Kusumoto, Chikusa, Nagoya 464-8650, Japan, Phone: +81-52-757-6785, Fax: +81-52-757-6799, E-mail:

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We thank Professor Ken-ichi Inui (Kyoto University Hospital, Kyoto, Japan) for kindly providing pBK-CMV plasmid vectors containing cDNA of rOAT1 and rOAT3.

Received: 2013-8-29
Accepted: 2013-10-9
Published Online: 2013-10-29
Published in Print: 2013-12-01

©2013 by Walter de Gruyter Berlin Boston

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