Effect of N-acetyl-cysteine and hyperoxia on erythropoietin production

Abstract

Previous studies in healthy subjects have shown an increase in erythropoietin (EPO) production after administration of N-acetyl-cysteine (NAC). These authors hypothesized that NAC increases intracellular reduced glutathione, decreasing reactive oxygen species and enabling EPO production. We investigated if EPO production could be stimulated with a single dose of NAC, after 90 min of pure oxygen breathing. Thirty-eight healthy volunteers were randomized into either the control (C) group or the NAC group, which received 600 mg NAC PO dissolved in a glass of orange juice, 60 min before breathing 15 L/min of 100% normobaric oxygen. Orange juice was administered to both groups. Blood samples for EPO measurement were taken at T0, before the orange juice administration, and T1, T2, T3 and T4, respectively, 8, 24, 32 and 48 h after the orange juice. The EPO concentrations of the NAC group decreased significantly at T1, followed by a significant increase compared to baseline, which was obvious until T4. The EPO concentrations of the C group did not show any significant variations. In this study, a significant increase of EPO production was observed after a short-term hyperoxic stimulus only when preceded with the administration of a single dose of NAC.

Acute short-term hyperoxia followed by mild hypoxia does not increase EPO production: resolving the “normobaric oxygen paradox”

“…Compared to the placebo, the IHH protocol induced a transient reduction in [EPO] within the initial 8 h following the IHH protocol. Our results thus present further evidence against the existence of NOP and concur with the findings of Keramidas et al (2011), McGuire et al (2006, and Momeni et al (2011).…”

“…In particular, subsequent studies either did not find augmented EPO production following an acute normobaric hyperoxic exposure (McGuire et al 2006;Momeni et al 2011) or have even shown a suppressive effect on EPO production (Keramidas et al 2011). This is in line with the results of previous studies showing the suppression of erythropoietic activity following normobaric hyperoxia in humans (Kokot et al 1994a, b).…”

Long‐term intermittent hyperoxic exposures do not enhance erythropoiesis

“…This theory conflicts with the reported O 2 -induced erythropoietic suppression in animals [5,6] and humans [7][8][9][10][11]. Keramidas et al [7] observed that a 2-h exposure to normobaric hyperoxia did not increase the production of [EPO] in healthy men during a single-blinded counter-balanced crossover investigation.…”

“…Thereafter, the plasma [EPO] levels appeared to resume their natural circadian rhythm [12,13]. Likewise, McGuire et al [10] and Momeni et al [11] failed to detect any significant differences in plasma [EPO] in healthy individuals after an acute O 2 breathing intervention.…”

Antioxidants may Attenuate Plasma Erythropoietin Decline after Hyperbaric Oxygen Diving

“…Water immersion may also result in elevated EPO plasma levels in healthy humans [6]. The EPO suppressing effect of hyperoxia may be mediated by free radicals [3,23]. N-acetyl-cysteine, a free radical scavenger, administered before exposure to reactive oxygen species e. g., under hyperoxic conditions, has been shown to increase EPO concentrations after an initial drop after exposure [23].…”