| Differential metabolomics for quantitative assessment of oxidative stress with strenuous exercise and nutritional intervention: thiol-specific regulation of cellular metabolism with N-acetyl-L-cysteine pretreatment. | |
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MedLine Citation:
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PMID: 20192244 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Despite several decades of active research, the success of large-scale clinical trials involving antioxidants remains equivocal given the complex biological interactions of reactive oxygen/nitrogen species in human health. Herein, we outline a differential metabolomics strategy by capillary electrophoresis-electrospray ionization-mass spectrometry (CE-ESI-MS) to assess the efficacy of nutritional intervention to attenuate oxidative stress induced by strenuous exercise. A healthy volunteer was recruited to perform a submaximal prolonged ergometer cycling trial until volitional exhaustion with frequent blood collection over a 6 h time interval, which included pre-, during, and postexercise periods while at rest. A follow-up study was subsequently performed by the same subject after high-dose oral intake of N-acetyl-L-cysteine (NAC) prior to performing the same exercise protocol under standardized conditions. Time-dependent changes in global metabolism of filtered red blood cell lysates by CE-ESI-MS were measured to reveal a significant attenuation of cellular oxidation associated with high-dose oral NAC intake relative to a control. Untargeted metabolite profiling allowed for the identification and quantification of several putative early- and late-stage biomarkers that reflected oxidative stress inhibition due to nutritional intervention, including oxidized glutathione (GSSG), reduced glutathione (GSH), 3-methylhistidine (3-MeHis), L-carnitine (C0), O-acetyl-L-carnitine (C2), and creatine (Cre). Our work demonstrates the proof-of-principle that NAC pretreatment is effective at dampening acute episodes of oxidative stress by reversible perturbations in global metabolism that can provide deeper insight into the mechanisms of thiol-specific protein inhibition relevant to its successful translation as a prophylaxis in clinical medicine. |
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Authors:
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Richard Lee; Daniel West; Stuart M Phillips; Philip Britz-McKibbin |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Analytical chemistry Volume: 82 ISSN: 1520-6882 ISO Abbreviation: Anal. Chem. Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-31 Completed Date: 2010-06-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370536 Medline TA: Anal Chem Country: United States |
Other Details:
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Languages: eng Pagination: 2959-68 Citation Subset: IM |
Affiliation:
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Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Canada. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetylcarnitine
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metabolism Acetylcysteine / pharmacology* Administration, Oral Carnitine / metabolism Electrophoresis, Capillary / methods* Exercise* Glutathione / metabolism Glutathione Disulfide / metabolism Humans Male Metabolomics / methods* Methylhistidines / metabolism Oxidative Stress* Reactive Oxygen Species / metabolism Spectrometry, Mass, Electrospray Ionization / methods* Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Methylhistidines; 0/Reactive Oxygen Species; 14992-62-2/Acetylcarnitine; 27025-41-8/Glutathione Disulfide; 368-16-1/3-methylhistidine; 541-15-1/Carnitine; 616-91-1/Acetylcysteine; 70-18-8/Glutathione |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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