Received for publication February 22, 2005.
Revised April 28, 2005.
Accepted for publication April 29, 2005.

The dietary polyphenol ellagic acid is a potent inhibitor of hOAT1

Abstract

Ellagic acid (EA), a polyphenol present in berries, has been demonstrated to be preventive of esophageal and colon cancer in animals. Here, we have studied the ability of organic anion transporters (OATs) and organic anion transporting polypeptides (OATPs) to transport EA. The accumulation of radiolabeled [¹⁴C]EA, [³H]p-aminohippuric acid (PAH), [¹⁴C]glutarate, [³H]estrone sulfate, [³H]ochratoxin A, and [³H]taurocholic acid ± inhibitor(s) was tested in OAT- and OATP-expressing oocytes. Oocytes expressing hOAT1, rOat1 and hOAT4 accumulated 6.5-, 7.1-, and 8.9-fold more EA than water-injected oocytes, respectively. This accumulation was prevented by the prototype OAT inhibitors bromosulfophthalein and probenecid. rOatp1, mOat2, hOAT3, and mOat5 showed no EA transport. The uptake of the prototype OAT substrate PAH in hOAT1-expressing oocytes was dose-dependently and potently inhibited by EA with an IC₅₀ of 207 nM. In conclusion, we have demonstrated that the OAT family members hOAT1, rOat1, and hOAT4 mediate transport of EA, with a very high affinity for hOAT1.

Key words: drug transport, drug-drug interactions, organic anion transport, renal elimination, transporters