Title

On The Antioxidant Properties Of Erythropoietin And Its Association With The Oxidative-Nitrosative Stress Response To Hypoxia In Humans

Keywords

Antioxidants; Erythropoietin; Free radicals; Hypoxia; Iron chelation

Abstract

Aim: The aim of this study was to examine if erythropoietin (EPO) has the potential to act as a biological antioxidant and determine the underlying mechanisms. Methods: The rate at which its recombinant form (rHuEPO) reacts with hydroxyl (HO˙), 2,2-diphenyl-1-picrylhydrazyl (DPPH˙) and peroxyl (ROO˙) radicals was evaluated in-vitro. The relationship between the erythopoietic and oxidative-nitrosative stress response to poikilocapneic hypoxia was determined separately in-vivo by sampling arterial blood from eleven males in normoxia and following 12 h exposure to 13% oxygen. Electron paramagnetic resonance spectroscopy, ELISA and ozone-based chemiluminescence were employed for direct detection of ascorbate (A˙-) and N-tert-butyl-α-phenylnitrone spin-trapped alkoxyl (PBN-OR) radicals, 3-nitrotyrosine (3-NT) and nitrite (NO2-). Results: We found rHuEPO to be a potent scavenger of HO˙ (kr = 1.03-1.66 × 1011 m-1 s-1) with the capacity to inhibit Fenton chemistry through catalytic iron chelation. Its ability to scavenge DPPH˙ and ROO˙ was also superior compared to other more conventional antioxidants. Hypoxia was associated with a rise in arterial EPO and free radical-mediated reduction in nitric oxide, indicative of oxidative-nitrosative stress. The latter was confirmed by an increased systemic formation of A˙-, PBN-OR, 3-NT and corresponding loss of NO2- (P < 0.05 vs. normoxia). The erythropoietic and oxidative-nitrosative stress responses were consistently related (r = -0.52 to 0.68, P < 0.05). Conclusion: These findings demonstrate that EPO has the capacity to act as a biological antioxidant and provide a mechanistic basis for its reported cytoprotective benefits within the clinical setting. Copyright

Publication Date

10-1-2014

Publication Title

Acta Physiologica

Volume

212

Issue

2

Number of Pages

175-187

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1111/apha.12313

Socpus ID

84912063924 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84912063924

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