Metabolomic search for uremic toxins as indicators of the effect of an oral sorbent AST-120 by liquid chromatography/tandem mass spectrometry

被引：109

作者：

Kikuchi, Kaori ^{[2
]}

Itoh, Yoshiharu ^{[2
]}

Tateoka, Ryoko ^{[2
]}

Ezawa, Atsuko ^{[2
]}

Murakami, Kenjiro ^{[2
]}

Niwa, Toshimitsu ^{[1
]}

机构：

[1] Nagoya Univ, Grad Sch Med, Dept Adv Med Uremia, Showa Ku, Nagoya, Aichi 4668550, Japan

[2] Kureha Corp, Biomed Res Labs, Tokyo, Japan

来源：

JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES | 2010年 / 878卷 / 29期

关键词：

Oral sorbent AST 120; Metabolome; Indoxyl sulfate; Uremic toxin; Chronic renal failure; Mass spectrometry; OSTEOBLAST-SPECIFIC PROTEINS; ORGANIC ANION TRANSPORTERS; INDOXYL SULFATE; P-CRESOL; OXIDATIVE STRESS; RENAL-FAILURE; PROGRESSION; EXPRESSION; PROLIFERATION; TGF-BETA-1;

D O I：

10.1016/j.jchromb.2010.09.006

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

An oral sorbent AST-120 composed of spherical porous carbon particles has superior adsorption ability for certain small-molecular-weight organic compounds known to accumulate in patients with chronic renal failure (CRF) A metabolomic approach was applied to search for uremic toxins as possible indicators of the effect of AST-120 Serum metabolites in normal and CRF rats before and after administration of AST-120 for 3 days were analyzed by liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) and principal component analysis Further serum and urine levels of the indicators were quantified by selected reaction monitoring of LC/ESI-MS/MS Indoxyl sulfate was the first principal serum metabolite which could differentiate CRF from both normal and AST-120-administered CRF rats followed by hippuric acid phenyl sulfate and 4-ethylphenyl sulfate CRF rats showed increased serum levels of indoxyl sulfate hippuric acid phenyl sulfate 4-ethylphenyl sulfate and p-cresyl sulfate Administration of AST-120 for 3 days to the CRF rats reduced the serum and urine levels of these metabolites In conclusion indoxyl sulfate is the best indicator of the effect of AST-120 in CRF rats Hippuric acid phenyl sulfate and 4-ethylphenyl sulfate are suggested as the additional indicators 4 Ethylphenyl sulfate is a newly identified uremic substance (C) 2010 Elsevier B V All rights reserved

引用

页码：2997 / 3002

页数：6

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