title: Green tea inhibited the elimination of nephro-cardiovascular toxins and deteriorated the renal function in rats with renal failure.
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.
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Yu-Hsuan
authors.initials: YH
authors.lastname: Peng
authors.affiliation: Department of Pharmaceutics, Virginia Commonwealth University, Richmond, U.S.A.
authors.forename: Douglas H
authors.initials: DH
authors.lastname: Sweet
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Shiuan-Pey
authors.initials: SP
authors.lastname: Lin
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Chung-Ping
authors.initials: CP
authors.lastname: Yu
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.
authors.forename: Pei-Dawn
authors.initials: PD
authors.lastname: Lee Chao
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan, R.O.C.|Department of Pharmacy, China Medical University Hospital, Taichung, Taiwan, R.O.C.|Department of Medical Research, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Hou
mesh_terms: D000225:Adenine / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D002392:Catechin / Q000032:analysis / Q000494:pharmacology; D003404:Creatinine / Q000097:blood; D003408:Cresols / Q000097:blood / Q000493:pharmacokinetics; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D020719:Glucuronides / Q000737:chemistry; D057809:HEK293 Cells; D006801:Humans; D007200:Indican / Q000097:blood / Q000493:pharmacokinetics; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D027362:Organic Anion Transport Protein 1 / Q000235:genetics / Q000378:metabolism; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051437:Renal Insufficiency / Q000378:metabolism / Q000473:pathology; D013431:Sulfates / Q000737:chemistry; D013463:Sulfuric Acid Esters / Q000097:blood / Q000493:pharmacokinetics; D013662:Tea / Q000737:chemistry* / Q000378:metabolism; D014118:Toxins, Biological / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003408:Cresols; D020719:Glucuronides; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; D013431:Sulfates; D013463:Sulfuric Acid Esters; D013662:Tea; D014118:Toxins, Biological; C114338:organic anion transport protein 3; C408690:4-cresol sulfate; D002392:Catechin; D003404:Creatinine; D000225:Adenine; D007200:Indican