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Stevia Rebaudiana Studies

Interactions of Stevioside and Steviol with Renal Organic Anion Transporters in S2 Cells and Mouse Renal Cortical Slices 2005  [PDF]

Purpose. Our previous studies have shown that both stevioside and steviol inhibited transepithelial transport of para-aminohippurate (PAH) in isolated rabbit renal proximal tubules by interfering with organic anion transport system. The current study examined the direct interactions of stevioside and steviol with specific organic anion transporters. Methods. S2 cells expressing human organic anion transporters (hOAT1, hOAT2, hOAT3, and hOAT4) and an intact renal epithelium were used to determine the inhibitory effect of stevioside and steviol on organic anion transport. Results. Stevioside at 0.5Y1 mM showed no interaction with any OAT. In contrast, steviol markedly inhibited substrate uptake in all S2hOAT cells. Steviol had low IC50 values for hOAT1 (11.4 mM) and hOAT3 (36.5 mM) similar to that of probenecid, whereas IC50 values for hOAT2 (1000 mM) and hOAT4 (285 mM) were much higher. Results obtained in mouse renal cortical slices were very similar; that is, stevioside was without inhibitory effect and steviol was a potent inhibitor of PAH and estrone sulfate (ES) transport. Conclusions. Stevioside has no interaction with human or mouse OATs. In contrast, steviol interacts directly with human OATs, in particular, hOAT1 and hOAT3, with a potency approximating probenecid, suggesting that the inhibition of OAT-mediated transport by steviol could alter renal drug clearance.


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