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Pushing arterial-venous plasma biomarkers to new heights : a model for personalised redox metabolomics?

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Cumpstey, Andrew F., Minnion, Magdalena, Fernandez, Bernadette O., Mikus-Lelinska, Monika, Mitchell, Kay, Martin, Daniel S., Grocott, Michael P. W. and Feelisch, Martin (2019) Pushing arterial-venous plasma biomarkers to new heights : a model for personalised redox metabolomics? Redox Biology, 21 . 101113. doi:10.1016/j.redox.2019.101113 ISSN 2213-2317.

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Official URL: http://dx.doi.org/10.1016/j.redox.2019.101113

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Abstract

The chemical and functional interactions between Reactive Oxygen (ROS), Nitrogen (RNS) and Sulfur (RSS) species allow organisms to detect and respond to metabolic and environmental stressors, such as exercise and altitude exposure. Whether redox markers and constituents of this ‘Reactive Species Interactome’ (RSI) differ in concentration between arterial and venous blood is unknown. We hypothesised that such measurements may provide useful insight into metabolic/redox regulation at the whole-body level and would be consistent between individuals exposed to identical challenges. An exploratory study was performed during the Xtreme Alps expedition in 2010 in which four healthy individuals (2 male, 2 female) underwent paired arterial and central venous blood sampling before, during and after performance of a constant-work-rate cardiopulmonary exercise test, at sea level and again at 4559 m. Unexpectedly, plasma total free thiol and free cysteine concentrations remained substantially elevated at altitude throughout exercise with minimal arteriovenous gradients. Free sulfide concentrations changed only modestly upon combined altitude/exercise stress, whereas bound sulfide levels were lower at altitude than sea-level. No consistent signal indicative of the expected increased oxidative stress and nitrate→nitrite→NO reduction was observed with 4-hydroxynonenal, isoprostanes, nitrate, nitrite, nitroso species and cylic guanosine monophosphate. However, the observed arteriovenous concentration differences revealed a dynamic pattern of response that was unique to each participant. This novel redox metabolomic approach of obtaining quantifiable ‘metabolic signatures’ to a defined physiological challenge could potentially offer new avenues for personalised medicine.

Item Type: Journal Article
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Journal or Publication Title: Redox Biology
Publisher: Elsevier
ISSN: 2213-2317
Official Date: February 2019
Dates:
DateEvent
February 2019Published
22 January 2019Available
14 January 2019Accepted
Volume: 21
Article Number: 101113
DOI: 10.1016/j.redox.2019.101113
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Contributors:
ContributionNameContributor ID
ResearcherThe Xtreme Alps research group, UNSPECIFIED

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