Document Detail

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.
MedLine Citation:
PMID:  20192244     Owner:  NLM     Status:  MEDLINE    
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.
Richard Lee; Daniel West; Stuart M Phillips; Philip Britz-McKibbin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Analytical chemistry     Volume:  82     ISSN:  1520-6882     ISO Abbreviation:  Anal. Chem.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-03-31     Completed Date:  2010-06-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370536     Medline TA:  Anal Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2959-68     Citation Subset:  IM    
Department of Chemistry and Chemical Biology, McMaster University, Hamilton, Canada.
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MeSH Terms
Acetylcarnitine / metabolism
Acetylcysteine / pharmacology*
Administration, Oral
Carnitine / metabolism
Electrophoresis, Capillary / methods*
Glutathione / metabolism
Glutathione Disulfide / metabolism
Metabolomics / methods*
Methylhistidines / metabolism
Oxidative Stress*
Reactive Oxygen Species / metabolism
Spectrometry, Mass, Electrospray Ionization / methods*
Young Adult
Reg. No./Substance:
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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