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

Toxins (Basel). 2012 Nov 14;4(11):1309-22. doi: 10.3390/toxins4111309.

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.

MeSH terms

  • Administration, Oral
  • Adsorption
  • Animals
  • Anions / blood
  • Carbon / administration & dosage
  • Carbon / chemistry
  • Carbon / therapeutic use*
  • Cations / blood
  • Disease Models, Animal
  • Electrophoresis, Capillary
  • Kidney Function Tests
  • Mass Spectrometry
  • Metabolome*
  • Metabolomics
  • Nephrectomy
  • Oxides / administration & dosage
  • Oxides / chemistry
  • Oxides / therapeutic use*
  • Rats
  • Rats, Wistar
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / metabolism
  • Toxins, Biological / blood*
  • Toxins, Biological / metabolism
  • Uremia / blood
  • Uremia / metabolism

Substances

  • Anions
  • Cations
  • Oxides
  • Toxins, Biological
  • Carbon
  • AST 120