A metabolomic approach to clarifying the effect of AST-120 on 5/6 nephrectomized rats by capillary electrophoresis with mass spectrometry (CE-MS).
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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DOI：
10.3390/toxins4111309
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发表时间：
2012-11-14
期刊：
影响因子：
4.2
通讯作者：
Abe T
中科院分区：
文献类型：
--
作者：
Akiyama Y;Takeuchi Y;Kikuchi K;Mishima E;Yamamoto Y;Suzuki C;Toyohara T;Suzuki T;Hozawa A;Ito S;Soga T;Abe T
口服吸附剂AST-120由球形碳颗粒组成，对慢性肾病（CKD）患者体内蓄积的某些小分子化合物具有吸附能力。到目前为止，已知很少有化合物在体内被AST-120吸附。为了检查AST-120在体内的作用，我们综合评估了146种化合物（61种阴离子和85种阳离子）在CKD模型大鼠中的血浆浓度，用或不用AST-120治疗四周。通过毛细管电泳和质谱，我们鉴定了6种阴离子和17种阳离子，它们被AST-120处理显著降低。相比之下，我们还鉴定了AST-120显著增加的2种阳离子。其中，除硫酸吲哚酚和马尿酸盐外，还有4种阴离子和19种阳离子是本研究中新发现的。与假手术组相比，CKD模型组血浆中N-乙酰神经氨酸、4-吡哆酸、4-氧戊酸、甘氨酸、γ-胍基丁酸、N-γ-乙基谷氨酰胺、尿囊素、胞嘧啶、5-甲基胞嘧啶和咪唑-4-乙酸的水平显著升高，AST-120治疗组血浆中这些物质的水平显著降低。因此，这10种化合物可以作为尿毒症化合物加入，表明AST-120治疗的效果。这项研究不仅为确定AST-120的指标提供了有用的信息，而且还为阐明AST-120治疗在临床环境中代谢谱的变化提供了有用的信息。
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.
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影响因子：
7.4
作者：
Soga, T;Heiger, DN
通讯作者：
Heiger, DN
影响因子：
5.7
作者：
Ueda, Seiji;Yamagishi, Sho-ichi;Okuda, Seiya
通讯作者：
Okuda, Seiya
影响因子：
4.4
作者：
Watala, Cezary;Kazmierczak, Piotr;Chlopicki, Stefan
通讯作者：
Chlopicki, Stefan
影响因子：
7.3
作者：
Chlopicki, S.;Swies, J.;Gebicki, J.
通讯作者：
Gebicki, J.
影响因子：
4.4
作者：
Soga, T;Ohashi, Y;Nishioka, T
通讯作者：
Nishioka, T