Metabolome Analysis of Erythrocytes from Patients with Chronic Hepatitis C Reveals the Etiology of Ribavirin-Induced Hemolysis

In the field of metabolomics, CE-MS is now regarded as a useful complementary analytical technique for the profiling of (highly) polar ionogenic metabolites in biological samples. Over the past few years, significant advancements have been made in CE-MS approaches for metabolic profiling studies. This paper, which is a follow-up of three previous review papers covering the years 2000-2012 [Electrophoresis 2009, 30, 276-291; Electrophoresis 2011, 32, 52-65; Electrophoresis 2013, 34, 86-98], provides an update of these developments covering the scientific literature from July 2012 to June 2014. Attention will be paid to novel interfacing techniques for coupling CE to MS and their implications for metabolomics studies. The potential of CEC-MS and MEKC-MS are also considered, and CE-MS systems for high-throughput metabolic profiling are discussed. The applicability of CE-MS for metabolomics studies is demonstrated by representative examples in the fields of biomedical, clinical, microbial, plant, environmental, and food metabolomics. An overview of recent CE-MS-based metabolomics studies is given in a table, which provides information on sample type and pretreatment, capillary coatings, and MS detection mode. Finally, general conclusions and perspectives are given.

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“…Details of the remaining CE‐MS‐based metabolomics applications of the past two years can be found in Table .…”

Section: Applicationsmentioning

confidence: 99%

CE‐MS for metabolomics: Developments and applications in the period 2012–2014

2014

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“…6 , our results revealed upregulated PPP in recovery processes of HAPC. Increased PPP could reduce NADP to NADPH, which plays an important role in regulating glutathione (GSH) and further protects against reactive oxygen species (ROS), repairs oxidized proteins of essential participants in carrying oxygen in RBC, promotes re-balance between pro-oxidants and antioxidants ( 16 , 17 ). Further, we validated our findings by comparing HAPC and control group directly and detected decreasing pentose phosphate pathway in HAPC subjects, which implied that PPP may be involved in the progression of hypoxia-induced erythrocytosis.…”

Section: Discussionmentioning

confidence: 99%

Elevated pentose phosphate pathway is involved in the recovery of hypoxia-induced erythrocytosis

Liu

Zhang

et al. 2017

Molecular Medicine Reports

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As a typical model of hypoxia-induced excessive erythrocytosis, high altitude polycythemia (HAPC) results in microcirculation disturbance, aggravates tissue hypoxia and results in a severe clinical outcome, without any effective intervention methods except for returning to an oxygen-rich environment. The present study aimed to explore potential therapeutic targets which may participate in the recovery of HAPC by studying the mechanisms of reducing the hemoglobin (HB) concentration during re-oxygenation. A total of 14 and 13 subjects were recruited over a 5,300 m distance and 5,170 m area. The patients were classified into HAPC or control groups based on their HB value. Plasma samples were collected on the day when they finished their stay in plateau for a year, and on the 180th day following their reaching in plain. Metabolic profiling was conducted by UPLC-QTOF/MS. MetaboAnalyst platform was performed to explore the most perturbed metabolic pathways. A panel of differential metabolites were obtained in the recovery phase of HAPC and control groups. The present study identified the uniquely upregulated pentose phosphate pathway in HAPC subjects, along with a significantly decreased HB level. The findings were verified via a direct comparison between HAPC and control subjects at a high altitude. An increased pentose phosphate pathway was identified in control groups compared with HAPC subjects. An elevated pentose phosphate pathway may therefore participate in the recovery of HAPC, whereas a downregulated pentose phosphate pathway may contribute to hypoxia-induced erythrocytosis. The results of the present study provide potential therapeutic strategies and novel insights into the pathogenesis of hypoxia-induced polycythemia.

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“…Importantly, CE also gives complementary information to HILIC [13], as well as, significantly better peak shape in many cases. It is therefore not surprising that CE-MS has already been considered for multiple metabolomics studies covering several applications, from aging [19], amino acid analysis [20,21] [46][47][48][49][50][51][52][53], CVD [54][55][56][57][58], diabetes [59][60][61][62][63][64][65], lifestyle [61][62][63][64][65][66][67][68][69][70][71], kidney disease [72,73], liver disease [74][75][76][77][78][79][80][81][82], the microbiome [83][84]…”

Section: Current Advantages and Biotechnology Applicationsmentioning

confidence: 99%

Capillary electrophoresis mass spectrometry based metabolomics

Buko¹

2017

J Appl Bioanal

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IntroductionSince its first formal definition more than a decade ago, metabolomics, or, the comprehensive analysis of all metabolites present within a biological system, has attracted growing interest in clinical research by academia, industry and government labs. This is most prevalent in biomarker and drug development applications where a considerable change has been witnessed in how new diagnoses, prognoses, and therapeutic options are being discovered and developed using omic technologies. Moreover, many chronic diseases suggest a strong metabolic involvement or even a clear metabolic cause, including cancer. Together with the other omic disciplines, including genomics and proteomics, metabolomics plays a key role in the implementation of personalized medicine; evidence-based medicine designed for individually designed healthcare strategies. In turn, biomarker discovery and the understanding of biochemical pathways typically rely on a multimodal approach. Among these modalities, there continues to be a growing interest in CE-MS based development and implementation in clinical development. Formulating the problemDepending on how you classify the metabolome, there is a complex chemical space separated by hydrophilicity, polarity and size, excluding a broad range of metabolites classified as lipids, separately referred to as lipidomics. This class of metabolites also covers a large range of physical properties for which specifically designed platforms work the best. For example, for years liquid chromatography-mass spectrometry (LC-MS) has been used to capture a host of hydrophilic and hydrophobic metabolites, while gas chromatography-mass spectrometry (GC-MS) has been used to capture small molecular weight metabolites. For this review, the metabolome refers to endogenous molecules with a molecular weight typically less than 1000 Kd. To measure, catalogue, and compare the entirety of the metabolic space, the implementation of comprehensive mass spectral databases was needed (e.g., Human Metab- Because of this diversity in physical properties and size of the metabolome in biological systems, there has been a need for the development of several analytical protocols based on different chromatographic methods to select specific subgroups of metabolites based on these different chemical properties beyond the technical capabilities of LC-MS and GC-MS. These new methods have their own advantages for selecting specific types of molecules: lipids, nucleotides, aminoacids or steroids. Nonmass spectrometric methods such as nuclear magnetic resonance (NMR) and non-chromatographic methods such as matrix-assisted laser desorption-time of flight (MALDI-TOF) imaging are successfully being used for selected metabolomic analyses. The focus of this review is recent publications that use CE-MS to extend the polar metabolome beyond what is observed by LC-MS and GC-MS. Metabolomics -current methods

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Metabolome Analysis of Erythrocytes from Patients with Chronic Hepatitis C Reveals the Etiology of Ribavirin-Induced Hemolysis

Cited by 11 publications

References 11 publications

CE‐MS for metabolomics: Developments and applications in the period 2012–2014

CE‐MS for metabolomics: Developments and applications in the period 2012–2014

Elevated pentose phosphate pathway is involved in the recovery of hypoxia-induced erythrocytosis

Capillary electrophoresis mass spectrometry based metabolomics

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