Effect of Normobaric Hypoxia on Alterations in Redox Homeostasis, Nitrosative Stress, Inflammation, and Lysosomal Function following Acute Physical Exercise

Abstract

Hypoxia is a recognized inducer of oxidative stress during prolonged physical activity. Nevertheless, previous studies have not systematically examined the effects of normoxia and hypoxia during acute physical exercise. The study is aimed at evaluating the relationship between enzymatic and nonenzymatic antioxidant barrier, total antioxidant/oxidant status, oxidative and nitrosative damage, inflammation, and lysosomal function in different acute exercise protocols under normoxia and hypoxia. Fifteen competitive athletes were recruited for the study. They were subjected to two types of acute cycling exercise with different intensities and durations: graded exercise until exhaustion (GE) and simulated 30 km individual time trial (TT). Both exercise protocols were performed under normoxic and hypoxic ( Fi O 2 = 16.5 % ) conditions. The number of subjects was determined based on our previous experiment, assuming the test power = 0.8 and α = 0.05 . We demonstrated enhanced enzymatic antioxidant systems during hypoxic exercise (GE: ↑ catalase (CAT), ↑ superoxide dismutase; TT: ↑ CAT) with a concomitant decrease in plasma reduced glutathione. In athletes exercising in hypoxia, redox status was shifted in favor of oxidation reactions (GE: ↑ total oxidant status, ↓ redox ratio), leading to increased oxidation/nitration of proteins (GE: ↑ advanced oxidation protein products (AOPP), ↑ ischemia-modified albumin, ↑ 3-nitrotyrosine, ↑ S-nitrosothiols; TT: ↑ AOPP) and lipids (GE: ↑ malondialdehyde). Concentrations of nitric oxide and its metabolites (peroxynitrite) were significantly higher in the plasma of hypoxic exercisers with an associated increase in inflammatory mediators (GE: ↑ myeloperoxidase, ↑ tumor necrosis factor-alpha) and lysosomal exoglycosidase activity (GE: ↑ N-acetyl-β-hexosaminidase, ↑ β-glucuronidase). Our study indicates that even a single intensive exercise session disrupts the antioxidant barrier and leads to increased oxidative and nitrosative damage at the systemic level. High-intensity exercise until exhaustion (GE) alters redox homeostasis more than the less intense exercise (TT, near the anaerobic threshold) of longer duration ( 20.2 ± 1.9 min vs. 61.1 ± 5.4 min—normoxia; 18.0 ± 1.9 min vs. 63.7 ± 3.0 min—hypoxia), while hypoxia significantly exacerbates oxidative stress, inflammation, and lysosomal dysfunction in athletic subjects.

May the Nitrosative and Carbonyl Stress Promote Inflammation in Patients with Colorectal Cancer?

“…Therefore, tumour cells exposed to hypoxia contain higher NO levels and its metabolites. 33 , 34 It is well known that NO may react rapidly to form peroxynitrite. Peroxynitrite may oxidize DNA and cause single-strand DNA breaks via an attack on the sugar-phosphate backbone, whereas other NO metabolites – N 2 O 3 may take part in nitrosation amines to form N-nitrosamines and then alkylate DNA.…”

Variation in glucose metabolism under acidified sodium nitrite mediated nitrosative stress in Saccharomyces cerevisiae

“…Hence, the observed phenomena were due to the nitrosative stress under our experimental condition. Changes in the redox homeostasis are a key marker of nitrosative stress (Kurutas, 2016; Maciejczyk et al, 2022). Under our experimental condition, an increased GSH/GSSG ratio, elevated concentration of GSH and reduced concentration of GSSG were observed, that in combination suggest that the treated cells responded by raising the intracellular reduced equivalent in the form of GSH (Astuti et al, 2016).…”

Reactive Oxygen Species and Antioxidant Interactions in Erythrocytes

“…However, under H 2 O 2 overproduction, CAT exhibits increased enzymatic activity, as measured by the Michaelis-Menten constant (Km). The Km for CAT (2.4 × 10 −4 M) is significantly greater than the Km for GPX (1 × 10 −6 M), which indicates that CAT scavenges H 2 O 2 efficiently at higher concentrations [101][102][103]. GPX is important in dealing with endogenous H 2 O 2 produced by Hb autoxidation, whereas CAT becomes increasingly important when erythrocytes are exposed to increased H 2 O 2 flux [15].…”