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Metabolomics analysis for hydroxy-L-proline-induced calcium oxalate nephrolithiasis in rats based on ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry.

ABSTRACT: About 80% of kidney stones are composed of calcium oxalate (CaOx) with variable amounts of calcium phosphate, and hyperoxaluria is considered as an important factor of CaOx nephrolithiasis. However, the underlying metabolic mechanisms of CaOx nephrolithiasis remain undefined. In this study, we successfully developed a rat model with hydroxy-L-proline (HLP) -induced CaOx nephrolithiasis. Rats were continuously orally administrated with HLP for 28 days. Urine and blood samples were collected from the rats treated with or without HLP at four different time points. UPLC-Q-TOF/MS was applied to profile the abundances of metabolites. To obtain more comprehensive analysis of metabolic profiling spectrum, combination of RP-LC and HILIC were applied. We identify 42 significant differential metabolites in the urine, and 13 significant differential metabolites in the blood. Pathway analysis revealed that the pathways involved in amino acid metabolism, taurine metabolism, bile acid synthesis, energy metabolism, TCA cycle, purine metabolism, vitamin metabolism, nicotinic acid and nicotinamide metabolism have been modulated by HLP treatment. This study suggested that a number of metabolic pathways are dysfunctional in the HLP induced crystal kidney injury, and further studies on those pathways are warranted to better understand the metabolic mechanism of CaOx nephrolithiasis.

SUBMITTER: Gao S

PROVIDER: S-EPMC4957101 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Metabolomics analysis for hydroxy-L-proline-induced calcium oxalate nephrolithiasis in rats based on ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry.

Gao Songyan S Yang Rui R Peng Zhongjiang Z Lu Hongtao H Li Na N Ding Jiarong J Cui Xingang X Chen Wei W Dong Xin X

Scientific reports 20160722

About 80% of kidney stones are composed of calcium oxalate (CaOx) with variable amounts of calcium phosphate, and hyperoxaluria is considered as an important factor of CaOx nephrolithiasis. However, the underlying metabolic mechanisms of CaOx nephrolithiasis remain undefined. In this study, we successfully developed a rat model with hydroxy-L-proline (HLP) -induced CaOx nephrolithiasis. Rats were continuously orally administrated with HLP for 28 days. Urine and blood samples were collected from ...[more]

PMID: 27443631

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Project description:BackgroundMetabolomics based on mass spectrometry analysis are increasingly applied in diverse scientific domains, notably agronomy and plant biology, in order to understand plants' behaviors under different stress conditions. In fact, these stress conditions are able to disrupt many biosynthetic pathways that include mainly primary metabolites. Profiling and quantifying primary metabolites remain a challenging task because they are poorly retained in reverse phase columns, due to their high polarity and acid-base properties. The aim of this work is to develop a simultaneous untargeted/targeted profiling of amino acids, organic acids, sulfur metabolites, and other several metabolites. This method will be applied on sulfur depleted barley, in order to study this type of stress, which is difficult to detect at early stage. Also, this method aims to explore the impact of this stress on barley's metabolome.ResultsUltra-high performance liquid chromatography-high resolution mass spectrometry-based method was successfully applied to real samples allowing to discriminate, detect, and quantify primary metabolites in short-runs without any additional sampling step such as derivatization or ion pairing. The retention of polar metabolites was successfully achieved using modified C18 columns with high reproducibility (relative standard deviation below 10%). The quantification method showed a high sensitivity and robustness. Furthermore, high resolution mass spectrometry detection provided reliable quantification based on exact mass, eliminating potential interferences, and allowing the simultaneous untargeted metabolomics analysis. The untargeted data analysis was conducted using Progenesis QI software, performing alignment, peak picking, normalization and multivariate analysis. The simultaneous analysis provided cumulative information allowing to discriminate between two plant batches. Thus, discriminant biomarkers were identified and validated. Simultaneously, quantification confirmed coherently the relative abundance of these biomarkers.ConclusionsA fast and innovated simultaneous untargeted/targeted method has successfully been developed and applied to sulfur deficiency on barley. This work opens interesting perspectives in both fundamental and applied research. Biomarker discovery give precious indication to understand plant behavior during a nutritional deficiency. Thus, direct or indirect measurement of these compounds allows a real time fertilization management and encounter the challenges of sustainable agriculture.

Dataset Information

Metabolomics analysis for hydroxy-L-proline-induced calcium oxalate nephrolithiasis in rats based on ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry.

Publications

Metabolomics analysis for hydroxy-L-proline-induced calcium oxalate nephrolithiasis in rats based on ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry.

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