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

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.

Oxidative Stress and Redox-Modulating Therapeutics in Inflammatory Bowel Disease

“…In line with these principles, ongoing exploration of the RSI should ideally follow an omic approach to identify central regulators and key determinants of the redox system that could be integrated with other single-omics datasets, ultimately leading to the identification of functionally relevant disease markers and treatment targets in IBD (Figure 3). By comparison with other layers of biological regulation, such redox-related omic approaches are at their infancy [83]. To some extent, this is due to several methodological constraints, such as the lack of sensitivity and specificity of available detection techniques, the fact that direct measurement of reactive species in intestinal cells or tissues is technically challenging because of their short biological half-lives, and that most techniques require highly sophisticated and expensive laboratory facilities [32,84].…”

Biomarkers in Stress Related Diseases/Disorders: Diagnostic, Prognostic, and Therapeutic Values

“…in arterial and venous circulation during metabolic and environmental stress. Such redox metabolic approaches were revealed with dynamic pattern of responses and variation in arterio-venous concentration of these metabolic signatures (Cumpstey et al, 2019).…”

Defining a role for exercise training in the management of asthma

“…Higher levels of oxidant stress markers have been demonstrated in children with asthma, and a reduction in these markers together with an increase in antioxidant enzyme activity and an improvement in lung function have been shown following an 8-week exercise training intervention [17]. Changes in the interactions between reactive oxygen species in healthy humans undergoing exercise intervention have been demonstrated [57], but this is yet to be investigated in adults with asthma. Additionally, mechanistic involvement of the glucocorticoid receptor does not necessarily fit with the findings of LU et al [38] when investigating he effect of exercise on glucocorticoid receptor expression in adolescents.…”