Metabolomic profiling of the autosomal dominant polycystic kidney disease rat model

Toyohara, Takafumi; Suzuki, Takehiro; Akiyama, Yasutoshi; Yoshihara, Daisuke; Takeuchi, Yoichi; Mishima, Eikan; Kikuchi, Kôichi; Suzuki, Chitose; Tanemoto, Masayuki; Ito, Sadayoshi; Nagao, Shizuko; Soga, Tomoyoshi; Abe, Takaaki

doi:10.1007/s10157-011-0467-4

Cited by 23 publications

(18 citation statements)

References 42 publications

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“…Importantly, our results are comparable with those of Taylor et al 14 . and Toyohara et al ., 15 who used metabolite profiling to investigate the cystic phenotype in jck mice and Cy/+ rats respectively, validating this approach as a means for identification of biomarkers of diagnostic and therapeutic potential.…”

Section: Discussionsupporting

confidence: 89%

Development of a non‐targeted metabolomics method to investigate urine in a rat model of polycystic kidney disease

Abbiss

Gummer²,

Sharman

et al. 2012

Nephrology

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Methods: Spot urine samples were collected from four male Lewis control and five male Lewis polycystic kidney rats aged 5 weeks, before kidney function was significantly impaired. Metabolites were extracted from urine and analysed using gas chromatography-mass spectrometry. Principal component analysis was used to determine key metabolites contributing to the variance observed between sample groups. Results:With the development of a metabolomics method to analyse Lewis and Lewis polycystic kidney rat urine, 2-ketoglutaric acid, allantoin, uric acid and hippuric acid were identified as potential biomarkers of cystic disease in the rat model. Conclusion:The findings of this study demonstrate the potential of metabolomics to further investigate kidney disease.Keywords: biomarker; gas chromatography; metabolite; polycystic kidney disease; urineThe advent of metabolomics, also termed metabolic profiling, has been in light of not only recent technological advancements in the separation and identification of low-molecular-weight molecules, but also in the software and hardware for processing the resultant large quantities of data.

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Section: Discussionsupporting

confidence: 89%

Development of a non‐targeted metabolomics method to investigate urine in a rat model of polycystic kidney disease

Abbiss

Gummer²,

Sharman

et al. 2012

Nephrology

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“…CE‐MS‐based metabolomics studies revealed important findings in the various application areas as outlined in this review. For example, the use of this approach revealed γ‐glutamyl dipeptides as novel biomarkers for liver diseases , serum glycerol‐3‐phospate as a marker for predicting glucose intolerance , provided insight into the cytotoxic mechanism of seleno‐methionine and insight into the storage conditions of various foods .…”

Section: Discussionmentioning

confidence: 99%

“…This approach has been used for various clinical metabolomics studies. For example, Toyohara et al used the CE‐MS approach of Soga (including use of a platinum sprayer needle) for comprehensive metabolic profiling of serum from an autosomal dominant polycystic kidney disease (ADPKD) rat model . In total 297 cationic and 190 anionic metabolites were detected in serum samples of this rat model and control rats, of which 21 cations and 19 anions accumulated significantly in the ADPKD rat model.…”

Section: Applicationsmentioning

confidence: 99%

CE‐MS for metabolomics: Developments and applications in the period 2010–2012

2012

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CE-MS has emerged as a powerful technique for the profiling of (highly) polar and charged metabolites in biological samples. This review provides an update of the most recent developments in CE-MS for metabolomics covering the scientific literature from July 2010 to June 2012. The present paper is an update of two previous review papers covering the years 2000-2010 (Electrophoresis 2009, 30, 276-291; Electrophoresis 2011, 32, 52-65). Emerging technological developments used in CE-MS for metabolomics are discussed, such as the use of novel interfacing techniques for coupling CE to MS. Representative examples illustrate the applicability of CE-MS in the fields of biomedical, clinical, microbial, plant, environmental and food metabolomics. Concerning targeted and non-targeted approaches, a comprehensive overview of recent CE-MS-based metabolomics studies is given in a table. Information on sample type and pretreatment, capillary coatings and MS detection mode is provided. Finally, general conclusions and perspectives are provided.

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“…In this study, using the CE-MS method [11,12,13,14,18], we comprehensively analyzed over 500 compounds and quantified 146 compounds (Supplementary Tables S1 and S2). We identified 25 compounds (6 anions and 19 cations) whose plasma concentrations were significantly changed by AST-120 treatment in 5/6Nx rats (the results are summarized in Figure 1 and Table 2).…”

Section: Discussionmentioning

confidence: 99%

“…A comprehensive and quantitative analysis of charged metabolites by CE-MS was performed [12,13,14]. Plasma (50 μL) was immediately plunged into methanol (450 μL) containing internal standards (20 μM each of methionine sulfone (Wako, Osaka Japan) for cations, MES (Dojindo, Kumamoto, Japan) and CSA (D-Camphol-10-sulfonic acid, Wako).…”

Section: Methodsmentioning

confidence: 99%

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

Akiyama

Takeuchi

Kikuchi

et al. 2012

Toxins

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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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Metabolomic profiling of the autosomal dominant polycystic kidney disease rat model

Abstract: We identified uremic retention solutes in ADPKD Cy/+ rats. Compounds related to ADPKD could be useful markers for detecting the early stage of ADPKD.

Cited by 23 publications

References 42 publications

Development of a non‐targeted metabolomics method to investigate urine in a rat model of polycystic kidney disease

Development of a non‐targeted metabolomics method to investigate urine in a rat model of polycystic kidney disease

CE‐MS for metabolomics: Developments and applications in the period 2010–2012

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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