Oxidative stress and nitric oxide metabolism responses during prolonged high-altitude exposure in preterm born adults

Prematurely-born individuals tend to exhibit higher resting oxidative stress, although evidence suggests they may be more resistant to acute hypoxia-induced redox balance alterations. We aimed to investigate the redox balance changes across a 3-day hypobaric hypoxic exposure at 3375 m in healthy adults born preterm (gestational age ≤ 32 weeks) and their term-born (gestational age ≥ 38 weeks) counterparts.

Resting venous blood was obtained in normoxia (prior to altitude exposure), immediately upon arrival to altitude, and the following 3 mornings. Antioxidant (superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and ferric reducing antioxidant power (FRAP)), pro-oxidant (xanthine oxidase (XO) and myeloperoxidase (MPO)) enzyme activity, oxidative stress markers (advanced oxidation protein product (AOPP) and malondialdehyde (MDA)), nitric oxide (NO) metabolites (nitrites, nitrates, and total nitrite and nitrate (NOx)), and nitrotyrosine were measured in plasma.

SOD increased only in the preterm group (p < 0.05). Catalase increased at arrival in preterm group (p < 0.05). XO activity increased at Day 3 for the preterm group, while it increased acutely (arrival and Day 1) in control group. MPO increased in both groups throughout the 3 days (p < 0.05). AOPP only increased at arrival in the preterm (p < 0.05) whereas it decreased at arrival up to Day 3 (p < 0.05) for control. MDA decreased in control group from arrival onward. Nitrotyrosine decreased in both groups (p < 0.05). Nitrites increased on Day 3 (p < 0.05) in control group and decreased on Day 1 (p < 0.05) in preterm group.

These data indicate that antioxidant enzymes seem to increase immediately upon hypoxic exposure in preterm adults. Conversely, the blunted pro-oxidant enzyme response to prolonged hypoxia exposure suggests that these enzymes may be less sensitive in preterm individuals. These findings lend further support to the potential hypoxic preconditioning effect of preterm birth.