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Toxins 2012, 4(11), 1309-1322; doi:10.3390/toxins4111309
Article

A Metabolomic Approach to Clarifying the Effect of AST-120 on 5/6 Nephrectomized Rats by Capillary Electrophoresis with Mass Spectrometry (CE-MS)

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1 Department of Community Health Promotion, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan 2 Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan 3 Department of Clinical Biology and Hormonal Regulation, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan 4 Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai 980-8573, Japan 5 Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan 6 Division of Medical Science, Tohoku University Graduate School of Biomedical Engineering, Sendai 980-8574, Japan
* Author to whom correspondence should be addressed.
Received: 18 July 2012 / Revised: 19 September 2012 / Accepted: 26 October 2012 / Published: 14 November 2012
(This article belongs to the Special Issue Uremic Toxins)
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Abstract

The oral adsorbent AST-120 is composed of spherical carbon particles and has an adsorption ability for certain small-molecular-weight compounds that accumulate in patients with chronic kidney disease (CKD). So far, very few compounds are known to be adsorbed by AST-120 in vivo. To examine the effect of AST-120 in vivo, we comprehensively evaluated the plasma concentrations of 146 compounds (61 anions and 85 cations) in CKD model rats, with or without four weeks of treatment with AST-120. By capillary electrophoresis with mass spectrometry, we identified 6 anions and 17 cations that were significantly decreased by AST-120 treatment. In contrast, we also identified 2 cations that were significantly increased by AST-120. Among them, 4 anions, apart from indoxyl sulfate and hippurate, and 19 cations were newly identified in this study. The plasma levels of N-acetyl-neuraminate, 4-pyridoxate, 4-oxopentanoate, glycine, γ-guanidinobutyrate, N-γ-ethylglutamine, allantoin, cytosine, 5-methylcytosine and imidazole-4-acetate were significantly increased in the CKD model compared with the sham-operated group, and were significantly decreased by AST-120 treatment. Therefore, these 10 compounds could be added as uremic compounds that indicate the effect of AST-120 treatment. This study provides useful information not only for identifying the indicators of AST-120, but also for clarifying changes in the metabolic profile by AST-120 treatment in the clinical setting.
Keywords: AST-120; uremic toxin; CE-MS AST-120; uremic toxin; CE-MS
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Akiyama, Y.; Takeuchi, Y.; Kikuchi, K.; Mishima, E.; Yamamoto, Y.; Suzuki, C.; Toyohara, T.; Suzuki, T.; Hozawa, A.; Ito, S.; Soga, T.; Abe, T. A Metabolomic Approach to Clarifying the Effect of AST-120 on 5/6 Nephrectomized Rats by Capillary Electrophoresis with Mass Spectrometry (CE-MS). Toxins 2012, 4, 1309-1322.

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