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

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

Acta physiologica (Oxford, England) (2014-05-09)
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
ABSTRACT

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. 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-). 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). 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Human ST2 / IL-33R ELISA Kit, for serum, plasma, cell culture supernatant and urine
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Human IL-12 p70 ELISA Kit, for serum, plasma, cell culture supernatant and urine
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Human EPO / Erythropoietin ELISA Kit, for serum, plasma, cell culture supernatants and urine
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Mouse IL-12 P40/70 ELISA Kit, for serum, plasma and cell culture supernatant
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