Metabolomic Biomarkers in a Model of Asthma Exacerbation

Saude, Erik J.; Obiefuna, Idongesit P.; Somorjai, Ray L.; Ajamian, Farnam; Skappak, Christopher; Ahmad, Taisir; Dolenko, Brion; Sykes, Brian D.; Moqbel, Redwan; Adamko, Darryl J.

doi:10.1164/rccm.200711-1716oc

Cited by 61 publications

(60 citation statements)

References 54 publications

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“…Metabolomics refers to the global investigation of metabolites in biological systems (comparing normal to disease) (Xu et al 2014), and has been applied to allergic asthma to profile metabolic changes and identify disease biomarkers (Lara et al 2008;Ho et al 2013Ho et al , 2014bSaude et al 2009Saude et al , 2011Mattarucchi et al 2012;Jung et al 2013). We have recently uncovered novel disease-relevant metabolic changes in the bronchoalveolar lavage fluid (BALF) from experimental mouse asthma, which involved major losses of sugars with resultant increases in energy metabolites and reductions of sterols (Ho et al , 2014b.…”

Section: Introductionmentioning

confidence: 99%

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

et al. 2014

Metabolomics

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The anti-malarial drug artesunate possesses anti-inflammatory and anti-oxidative actions in experimental asthma, comparable to corticosteroid. We hypothesized that artesunate may modulate disease-relevant metabolic alterations in allergic asthma. To explore metabolic profile changes induced by artesunate in allergic airway inflammation, we analysed bronchoalveolar lavage fluid (BALF) and serum from naïve and ovalbumininduced asthma mice treated with artesunate, using both gas and liquid chromatography-mass spectrometry metabolomics. Pharmacokinetics analyses of serum and lung tissues revealed that artesunate is rapidly converted into the active metabolite dihydroartemisinin. Artesunate effectively suppressed BALF total and differential counts, and repressed BALF Th2 cytokines, IL-17, IL-12(p40), MCP-1 and G-CSF levels. Artesunate had no effects on both BALF and serum metabolome in naïve mice. Artesunate promoted restoration of BALF sterols (cholesterol, cholic acid and cortol), phosphatidylcholines and carbohydrates (arabinose, mannose and galactose) and of serum 18-oxocortisol, galactose, glucose and glucouronic acid in asthma. Artesunate prevented OVA-induced increases in pro-inflammatory metabolites from arginine-proline metabolic pathway, particularly BALF levels of urea and alanine and serum levels of urea, proline, valine and homoserine. Multiple statistical correlation analyses revealed association between altered BALF and serum metabolites and inflammatory cytokines. Dexamethasone failed to reduce Wanxing Eugene Ho and Yong-Jiang Xu have contributed equally to this work.Electronic supplementary material The online version of this article (doi:10.1007/s11306-014-0699-x) contains supplementary material, which is available to authorized users. Metabolomics (2015) 11:380-390 DOI 10.1007 urea level and caused widespread changes in metabolites irrelevant to asthma development. Here we report the first metabolome profile of artesunate treatment in experimental asthma. Artesunate restored specific metabolic perturbations in airway inflammation, which correlated well with its anti-inflammatory actions. Our metabolomics findings further strengthen the therapeutic value of using artesunate to treat allergic asthma.

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Section: Introductionmentioning

confidence: 99%

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

et al. 2014

Metabolomics

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“…1 H nuclear magnetic resonance (NMR) spectroscopy analysis of biofluids provides a potential tool for understanding biochemical processes associated with diseases [11][12][13][14]. 1 H NMR spectroscopy by means of high-resolution magic-angle spinning (HR-MAS) is an excellent option to study intact tissues [15][16][17][18][19][20][21][22][23]. In a previous study, Lin et al [22] constructed a model based on analysis of serum samples for early diagnostic evaluation in an experimental model of sepsis that achieved prediction accuracy of 87%.…”

Section: Introductionmentioning

confidence: 99%

A metabolomic approach for diagnosis of experimental sepsis

et al. 2011

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“…As such, metabolomics has been comprehensively applied in physiology, disease, and toxicology research fields [26] . Nuclear magnetic resonance (NMR) spectroscopy [27] , liquid chromatography coupled mass spectrometry (LC-MS) [28] , gas chromatography coupled mass spectrometry (GC-MS) [29] , and Fourier transform mass spectrometry [30] have been successfully used to obtain metabolomic data. GC coupled to a time-of-flight mass analyzer (GC-TOF/ MS) provides an improvement over conventional GC-MS analysis due to its high scan rates and the availability of mathematic algorithms to deconvolute closely overlapping peaks.…”

Section: Introductionmentioning

confidence: 99%

GC-TOF/MS-based metabolomic profiling of estrogen deficiency-induced obesity in ovariectomized rats

Zhang

Wang

et al. 2011

Acta Pharmacol Sin

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Aim: To explore the alteration of endogenous metabolites and identify potential biomarkers using metabolomic profiling with gas chromatography coupled a time-of-flight mass analyzer (GC/TOF-MS) in a rat model of estrogen-deficiency-induced obesity. Methods: Twelve female Sprague-Dawley rats six month of age were either sham-operated or ovariectomized (OVX). Rat blood was collected, and serum was analyzed for biomarkers using standard colorimetric methods with commercial assay kits and a metabolomic approach with GC/TOF-MS. The data were analyzed using multivariate statistical techniques. Results: A high body weight and body mass index inversely correlated with serum estradiol (E2) in the OVX rats compared to the sham rats. Estrogen deficiency also significantly increased serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol. Utilizing GC/TOF-MS-based metabolomic analysis and the partial least-squares discriminant analysis, the OVX samples were discriminated from the shams. Elevated levels of cholesterol, glycerol, glucose, arachidonic acid, glutamic acid, glycine, and cystine and reduced alanine levels were observed. Serum glucose metabolism, energy metabolism, lipid metabolism, and amino acid metabolism were involved in estrogen-deficiency-induced obesity in OVX rats. Conclusion: The series of potential biomarkers identified in the present study provided fingerprints of rat metabolomic changes during obesity and an overview of multiple metabolic pathways during the progression of obesity involving glucose metabolism, lipid metabolism, and amino acid metabolism.

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Metabolomic Biomarkers in a Model of Asthma Exacerbation

Abstract: Urine metabolites correlate with airway dysfunction in an asthma model. Urine NMR analysis is a promising, noninvasive technique for monitoring asthma in humans.

Cited by 61 publications

References 54 publications

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

Anti-malarial drug artesunate restores metabolic changes in experimental allergic asthma

A metabolomic approach for diagnosis of experimental sepsis

GC-TOF/MS-based metabolomic profiling of estrogen deficiency-induced obesity in ovariectomized rats

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