The Clinical Application of Purine Nucleosides As Biomarkers of Tissue Ischemia and Hypoxia in Humans In Vivo

Abstract

During periods of ischemia and hypoxia, intracellular adenosine triphosphate stores are rapidly depleted. Its metabolism results in release of purine nucleosides into the systemic circulation. While the potential of purine nucleosides as a biomarker of ischemia has long been recognized, this has been limited by their complex physiological role and inherent instability leading to problematic sampling and prolonged, complex analysis procedures. Purine release has been demonstrated from cerebral tissue in patients undergoing carotid endarterectomy and patients presenting to hospital with stroke and transient ischemic attack. Rises in purine nucleosides have also been demonstrated in patients with angina and myocardial infarction, during systemic hypoxia, exercise, in patients with peripheral arterial disease and during surgery. This article reviews purine nucleoside production in ischemia, the development of purine analysis technology and details results of the studies investigating purine nucleosides as a biomarker of ischemia with suggestions for areas of future research.

Understanding the pathophysiological changes via untargeted metabolomics in COVID‐19 patients

“…Inflammation and hypoxia induce the release of ATP from intracellular stores to extracellular space, and then it is converted to adenosine monophosphate (AMP), which is then metabolized to adenosine and three phosphates. Finally, adenosine is converted to inosine and hypoxanthine by activating adenosine deaminase and purine nucleoside phosphorylase, respectively 11–14 . Hypoxanthine concentration in blood is found to be a sensitive parameter of hypoxia 13,15 .…”

Purines: From Diagnostic Biomarkers to Therapeutic Agents in Brain Injury

“…This brain to blood efflux of adenosine and its metabolites, inosine and hypoxanthine, all of which share the same transporter (SLC29) [13] results in the appearance in blood of purines above their usual baseline levels during cerebral metabolic stress and trauma [54] .…”

“…These often include blockers of adenosine deaminase, and inhibitors of the equilibrative transporters in a "stopping" solution prior to separation of plasma for analysis. The widespread adoption of purines as a diagnostic tool thus needs rapid point of care measurements [54] .…”

Hypoxanthine is a pharmacodynamic marker of ischemic brain edema modified by glibenclamide

“…As such, elevated hypoxanthine has been demonstrated to be a marker of hypoxia in several disease states. 24 , 25 , 26 Interestingly, the oxidation of hypoxanthine and xanthine by XO also produces reactive oxygen species (ROS) 27 and triggers cytotoxicity. 28 In healthy non-ischemic cells, XO exists predominantly as xanthine dehydrogenase (XD), which uses NAD+ instead of O 2 as a cofactor.…”