A Metabolomic approach to clarifying the effect of AST-120 on 5/6 nephrectomized rats by capillary electrophoresis with mass spectrometry (CE-MS)

Yasutoshi Akiyama, Yoichi Takeuchi, Koichi Kikuchi, Eikan Mishima, Yasuaki Yamamoto, Chitose Suzuki, Takafumi Toyohara, Takehiro Suzuki, Atsushi Hozawa, Sadayoshi Ito, Tomoyoshi Soga, Takaaki Abe

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24 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1309-1322
Number of pages14
JournalToxins
Volume4
Issue number11
DOIs
Publication statusPublished - 2012 Nov

Keywords

  • AST-120
  • CE-MS
  • Uremic toxin

ASJC Scopus subject areas

  • Toxicology
  • Health, Toxicology and Mutagenesis

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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. (2012). A Metabolomic approach to clarifying the effect of AST-120 on 5/6 nephrectomized rats by capillary electrophoresis with mass spectrometry (CE-MS). Toxins, 4(11), 1309-1322. https://doi.org/10.3390/toxins4111309