On the antioxidant properties of erythropoietin and its association with the oxidative-nitrosative stress response to hypoxia in humans

D M Bailey, C Lundby, R M G Berg, S Taudorf, H Rahmouni, M Gutowski, C W Mulholland, J L Sullivan, E R Swenson, J McEneny, I S Young, B K Pedersen, K Møller, S Pietri, M Culcasi

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10 Citations (Scopus)


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 × 10(11) 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.

Original languageEnglish
Pages (from-to)175-87
Number of pages13
JournalActa Physiologica
Issue number2
Publication statusPublished - 8 May 2014


  • Adult
  • Antioxidants
  • Electron Spin Resonance Spectroscopy
  • Enzyme-Linked Immunosorbent Assay
  • Erythropoietin
  • Humans
  • Hypoxia
  • Luminescence
  • Male
  • Nitrosation
  • Oxidative Stress


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