On the antioxidant properties of erythropoietin and its association with the oxidative–nitrosative stress response to hypoxia in humans
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On the antioxidant properties of erythropoietin and its association with the oxidative–nitrosative stress response to hypoxia in humans. / Bailey, D M; Lundby, C; Berg, R M G; Taudorf, S; Rahmouni, H; Gutowski, M; Mulholland, C W; Sullivan, J L; Swenson, E R; McEneny, J; Young, I S; Pedersen, Bente Klarlund; Møller, Kirsten; Pietri, S; Culcasi, M.
In: Acta Physiologica (Print), Vol. 212, No. 2, 2014, p. 175-187.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - On the antioxidant properties of erythropoietin and its association with the oxidative–nitrosative stress response to hypoxia in humans
AU - Bailey, D M
AU - Lundby, C
AU - Berg, R M G
AU - Taudorf, S
AU - Rahmouni, H
AU - Gutowski, M
AU - Mulholland, C W
AU - Sullivan, J L
AU - Swenson, E R
AU - McEneny, J
AU - Young, I S
AU - Pedersen, Bente Klarlund
AU - Møller, Kirsten
AU - Pietri, S
AU - Culcasi, M
N1 - © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
KW - Adult
KW - Anoxia
KW - Antioxidants
KW - Electron Spin Resonance Spectroscopy
KW - Enzyme-Linked Immunosorbent Assay
KW - Erythropoietin
KW - Humans
KW - Luminescence
KW - Male
KW - Nitrosation
KW - Oxidative Stress
U2 - 10.1111/apha.12313
DO - 10.1111/apha.12313
M3 - Journal article
C2 - 24811856
VL - 212
SP - 175
EP - 187
JO - Acta Physiologica
JF - Acta Physiologica
SN - 1748-1708
IS - 2
ER -
ID: 138420195