Manipulation of systemic oxygen flux by acute exercise and normobaric hypoxia: implications for reactive oxygen species generation

Abstract

Maximal exercise in normoxia results in oxidative stress due to an increase in free radical production. However, the effect of a single bout of moderate aerobic exercise performed in either relative or absolute normobaric hypoxia on free radical production and lipid peroxidation remains unknown. To examine this, we randomly matched {according to their normobaric normoxic VO2peak [peak VO2 (oxygen uptake)]} and assigned 30 male subjects to a normoxia (n = 10), a hypoxia relative (n = 10) or a hypoxia absolute (n = 10) group. Each group was required to exercise on a cycle ergometer at 55% of VO2peak for 2 h double-blinded to either a normoxic or hypoxic condition [FiO2 (inspired fraction of O2) = 0.21 and 0.16 respectively]. ESR (electron spin resonance) spectroscopy in conjunction with ex vivo spin trapping was utilized for the direct detection of free radical species. The main findings show that moderate intensity exercise increased plasma-volume-corrected free radical and lipid hydroperoxide concentration (pooled rest compared with exercise data, P < 0.05); however, there were no selective differences between groups (statexgroup interaction, P > 0.05). The delta change in free radical concentration was moderately correlated with systemic VO2 (r2 = 0.48, P < 0.05). The hyperfine coupling constants recorded from the ESR spectra [aN = 13.8 Gauss, and a(H)beta = 1.9 Gauss; where 1 Gauss = 10(-4) T (telsa)] are suggestive of oxygen-centred free radical species formed via the decomposition of lipid hydroperoxides. Peripheral leucocyte and neutrophil cells and total CK (creatine kinase) activity all increased following sustained exercise (pooled rest compared with exercise data, P < 0.05), but no selective differences were observed between groups (state x group interaction, P > 0.05). We conclude that a single bout of moderate aerobic exercise increases secondary free radical species. There is also evidence of exercise-induced muscle damage, possibly caused by the increase in free radical generation.

Exercise‐induced lipid peroxidation: Implications for deoxyribonucleic acid damage and systemic free radical generation

“…The significant positive correlation between DNA damage and PBN-adduct provides a tentative association and link between the two molecules. Alkoxyl radicals are derived from oxidative damage to lipid cellular membranes via metal-catalyzed reactions [Davison et al, 2006]. All hyperfine coupling constants measured in the present investigation are synonymous with the detection of alkoxyl radicals (a N 5 13.7 G and ab H 5 1.8 G) and are consistent with published data [Davison et al, 2006[Davison et al, , 2008.…”

“…Alkoxyl radicals are derived from oxidative damage to lipid cellular membranes via metal-catalyzed reactions [Davison et al, 2006]. All hyperfine coupling constants measured in the present investigation are synonymous with the detection of alkoxyl radicals (a N 5 13.7 G and ab H 5 1.8 G) and are consistent with published data [Davison et al, 2006[Davison et al, , 2008. The systemic increase in the alkoxyl free radical concentration and LOOH following incremental exercise along with the positive correlation may suggest free radical-mediated damage to DNA following a short bout of moderate-and high-intensity exercise.…”

Exercise training protects the LDL I subfraction from oxidation susceptibility in an aged human population

“…The method of Altman [16] was used to determine the number of subjects (n ¼ 28, excluding a 20% drop out rate) required for this study (using previously published lipid data, [17]). Data were analysed using parametric statistics following confirmation of a normal distribution by Shapiro Wilks tests.…”

Hypoxia and oxidation levels of DNA and lipids in humans and animal experimental models

“…Sequential study designs are also used to a great extent in investigations of hypoxia by exposure in chambers or masks (42)(43)(44)(45)(46), but there are also well-controlled studies (47)(48)(49)(50)(51). Four of the well-controlled studies reported a relationship between exposure to hypoxia and oxidative damage to both DNA and lipids (47,48,50,51), whereas one investigation found no effect of hypoxia (49). Data based on sequential studies indicate hypoxia-induced effects on at least one biomarker of lipid or DNA oxidation (12-16, 20, 23, 24, 34-42, 45, 46), except two studies that happens to be short-term (less than 10 min) exposure to hypoxia (43,44).…”

“…For instance, oxygen level decreased over time in studies of the ascend to the summit of San Pedro y San Pablo volcano (46) and the simulated ascend to Mt Everest (37), but it is impossible to split the time component from the effect of hypoxia. Figure 1 outlines the results of an overall analysis where studies have been stratified into those with exposures lasting 1 h or less (43)(44)(45)48), between 1 and 24 h (16,42,46,47,50,51), and between 24 h and 8 weeks (12-16, 20, 23, 34-41). This analysis indicates that the effect observed after days or weeks of hypoxia is larger than at earlier time point, but it should also be recognized that most of these studies are poorly controlled and it may just be an effect of confounding factors.…”