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

doi:10.3390/toxins4111309

Yasutoshi Akiyama, Takaaki Abe + Show 10 more

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https://doi.org/10.3390/toxins4111309

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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.

Highlights

Chronic kidney disease (CKD) is a global health problem that carries a substantial risk for cardiovascular morbidity and death [1,2]
There were no significant differences in the total amounts of food intake, SBP, BW, Cr and Ccr between the control and AST-120 groups throughout the experiment (Table 1)
AST-120 rat died of uremia at three weeks

Summary

Introduction

Chronic kidney disease (CKD) is a global health problem that carries a substantial risk for cardiovascular morbidity and death [1,2]. The only established therapy to eliminate uremic toxins in CKD patients is AST-120 [6,7]. It is reported that AST-120 inhibits the progression of CKD and cardiovascular diseases [6]. One of the best-known uremic toxins whose plasma level is decreased by AST-120 treatment is indoxyl sulfate [8]. AST-120 decreases the plasma level of indoxyl sulfate by adsorbing the precursor of indoxyl sulfate, i.e., the indole, resulting in the reduction of indoxyl sulfate production in the liver. In addition to indoxyl sulfate, some compounds whose plasma levels are decreased by AST-120 treatment have been reported, such as hippurate, phenyl sulfate, 4-ethylphenyl sulfate, p-cresyl sulfate [9] and advanced glycation end products [10]. The target compounds of AST-120 have not been fully elucidated

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