Metabolomic search for uremic toxins as indicators of the effect of an oral sorbent AST-120 by liquid chromatography/tandem mass spectrometry.
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.
Kikuchi
Kaori
K
Biomedical Research Laboratories, Kureha Corporation, Tokyo, Japan.
Itoh
Yoshiharu
Y
Tateoka
Ryoko
R
Ezawa
Atsuko
A
Murakami
Kenjiro
K
Niwa
Toshimitsu
T
D000327:Adsorption; D000818:Animals; D002244:Carbon / Q000008:administration & dosage* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D006626:Hippurates / Q000097:blood / Q000378:metabolism / Q000652:urine; D007200:Indican / Q000097:blood / Q000378:metabolism / Q000652:urine; D007676:Kidney Failure, Chronic / Q000097:blood / Q000378:metabolism / Q000628:therapy* / Q000652:urine; D008297:Male; D055432:Metabolomics; D010087:Oxides / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014118:Toxins, Biological / Q000097:blood* / Q000378:metabolism / Q000652:urine*; D014511:Uremia / Q000097:blood / Q000378:metabolism / Q000628:therapy* / Q000652:urine
D006626:Hippurates; D010087:Oxides; D014118:Toxins, Biological; D002244:Carbon; C040896:AST 120; D007200:Indican; C030514:hippuric acid