(-)-Epigallocatechin-3-gallate Inhibits Human and Rat Renal Organic Anion Transporters

Organic anion transporter 1 (OAT1, SLC22A6) and 3 (OAT3, SLC22A8) are multispecific drug transporters highly expressed on the basolateral membranes of the renal proximal tubules. OAT1 and OAT3 mediate the tubular secretion of clinically significant drugs; thus, they influence the pharmacokinetics of drugs and further determine their efficacy and toxicity. OAT1 and OAT3 are also the target of drug-drug interactions. In this study, we examined the effects of the tea catechin (-)-epigallocatechin-3-gallate (EGCG) on human (h) and rat (r) OAT1 and OAT3 using the fluorescent organic anion 6-carboxyfluorescein (6-CF) and hOAT1-, hOAT3-, rOat1-, or rOat3-expressing HEK293 cells and on renal elimination of 6-CF in rats. 6-CF is transported by hOAT1, hOAT3, rOat1, and rOat3. 6-CF is urinary excreted by Oats in rats. EGCG, a dominant catechin in green tea leaf, inhibits human and rat OAT1 and OAT3 and reduces the renal elimination of 6-CF in rats. Our findings are useful for the assessment of food-drug interactions mediated by renal OATs.

Automated summary

OAT1 and OAT3 are highly expressed drug transporters in the renal proximal tubules, affecting drug metabolism and toxicity, and are also susceptible to drug-drug interactions. The tea catechin EGCG inhibits OAT1 and OAT3, reducing the renal elimination of 6-CF in rats.