Moderate hypoxia/hyperoxia attenuates acute hypoxia-induced oxidative damage and improves antioxidant defense in lung mitochondria.

A new mode of adaptive training was explored, which combines periods of hypoxia and hyperoxia (H/H) and is characterized by upregulation of adaptive ROS signals compared to classical intermittent hypoxic training. The purpose of this study was to determine the influence of repetitive moderate sessions of hypoxia and hyperoxia on pro-/antioxidant homeostasis in lung mitochondria of rats exposed to acute severe hypoxia. It was shown that H/H pretreatment [5 cycles of 5 min hypoxia (10% O2 in N2) alternated with 5 min hyperoxia (30% O2 in N2) daily for two weeks] reduced the acute hypoxia-induced basal and stimulated in vitro lipid peroxidation, increased the GSH/GSSG ratio, and decreased the GSSG content. The enhancement in the level of GSH and activities of MnSOD, GPx and GR in comparison with acute hypoxia as well as the maintenance of GST activity at control level confirm that mitochondrial protection during H/H may be mediated through the modulation of mitochondrial antioxidant levels. In lung H/H training caused the increase in MnSOD protein synthesis, at the same time, no changes in mRNA MnSOD expression was registered. This study supports the viewpoint that moderate periodic generation of free radical signal during changes in the oxygen level causes the induction of antioxidant enzyme protein synthesis that may be an important trigger for specific adaptations.