Green tea inhibited the elimination of nephro-cardiovascular toxins and deteriorated the renal function in rats with renal failure

Yu-Hsuan Peng,Yu-Chi Hou,Shiuan-Pey Lin,Douglas H Sweet,Chung-Ping Yu,Pei-Dawn Lee Chao

doi:10.1038/srep16226

Abstract

Chronic kidney disease (CKD) is a major health problem worldwide. Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are highly protein-bound nephro-cardiovascular toxins, which are not efficiently removed through hemodialysis. The renal excretions of IS and PCS were mediated by organic anion transporters (OATs) such as OAT1 and OAT3. Green tea (GT) is a popular beverage containing plenty of catechins. Previous pharmacokinetic studies of teas have shown that the major molecules present in the bloodstream are the glucuronides/sulfates of tea catechins, which are putative substrates of OATs. Here we demonstrated that GT ingestion significantly elevated the systemic exposures of endogenous IS and PCS in rats with chronic renal failure (CRF). More importantly, GT also significantly increased the levels of serum creatinine (Cr) and blood urea nitrogen (BUN) in CRF rats. Mechanism studies indicated that the serum metabolites of GT (GTM) inhibited the uptake transporting functions of OAT1 and OAT3. In conclusion, GT inhibited the elimination of nephro-cardiovascular toxins such as IS and PCS, and deteriorated the renal function in CRF rats.

Highlights

Chronic kidney disease (CKD) is a major health problem worldwide
Owing to the acidic properties, indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are existing as anions under physiological pH in the systemic circulation, and the uptake transports of IS and PCS across the cell membranes of renal proximal tubules were mediated by organic anion transporters (OATs) such as OAT1 and OAT38–10
For mimicking the molecules interacting with OAT1 and OAT3 located on the membrane of renal proximal tubular cells, GTM was prepared from rats after receiving Green tea (GT) infusion

Summary

Introduction

Chronic kidney disease (CKD) is a major health problem worldwide. Indoxyl sulfate (IS) and p-cresyl sulfate (PCS) are highly protein-bound nephro-cardiovascular toxins, which are not efficiently removed through hemodialysis. Previous pharmacokinetic studies of teas have shown that the major molecules present in the bloodstream are the glucuronides/sulfates of tea catechins, which are putative substrates of OATs. Here we demonstrated that GT ingestion significantly elevated the systemic exposures of endogenous IS and PCS in rats with chronic renal failure (CRF). Mechanism studies indicated that the serum metabolites of GT (GTM) inhibited the uptake transporting functions of OAT1 and OAT3. We hypothesized that the serum metabolites of GT (GTM) might inhibit the uptake transport of IS and PCS across the cell membrane of renal proximal tubule mediated by OAT1 and OAT3, which in turn would lead to elevated blood levels of IS and www.nature.com/scientificreports/. Previous studies have reported that adenine-induced chronic renal failure (CRF) rats showed lower protein expressions of OAT1 and OAT3 along with the decreased clearance of IS and PCS19,23. Cell models were used to verify the involvement of OAT1 and OAT3 in the mechanism

Methods

Results

Conclusion