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

Toxins

Yasutoshi Akiyama³  Yoichi Takeuchi⁴  Koichi Kikuchi⁴  Eikan Mishima⁴  Yasuaki Yamamoto⁴  Chitose Suzuki⁴  Takafumi Toyohara⁴  Takehiro Suzuki⁴  Atsushi Hozawa²  Sadayoshi Ito⁴  Tomoyoshi Soga¹ 

[1] Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan;Department of Preventive Medicine and Epidemiology, Tohoku Medical Megabank Organization, Tohoku University, Sendai 980-8573, Japan;Department of Community Health Promotion, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan;Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574, Japan;

关键词: AST-120;    uremic toxin;    CE-MS;   

DOI  :  10.3390/toxins4111309

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.