Intermittent hyperbaric oxygen exposure mobilizing peroxiredoxin 6 to prevent oxygen toxicity Abstract Intermittent hyperbaric oxygen exposure (IE-HBO) can protect the body against oxygen toxicity, but the underlying mechanisms are not very clear. Peroxiredoxin 6 (Prdx6) is a special endogenous antioxidative protein. We explored if the protective effects of IE-HBO are related to Prdx6. Mice were exposed to 280 kPa O2 for 60 min, followed by 30-min exposure to 20% O2/N2 mixture with equal pressure, repeated for six cycles. The Prdx6 protein level and non-selenium glutathione peroxidase (NSGPx) activity in the brain and lungs were then measured and the injury degree of lung and the oxidation level of brain and lung were evaluated. On this basis, the relationship between Prdx6 and IE-HBO’s protection was explored. Generally, both IE-HBO and continuous exposure to HBO (CE-HBO) could increase the protein and mRNA levels of Prdx6, and such increases were more significant 24 h after cessation of exposure; moreover, the Prdx6 level of IE-HBO was higher than that of CE-HBO in both brain and lung, also more significantly 24 h after cessation of exposure. In addition, IE-HBO exposure could more effectively potentiate the activity of NSGPx and increase GSH content in brain and lung tissues. At the same time, it could reduce oxidation products in these tissues. IE-HBO could also provide protection for the lungs against injuries resulting from prolonged HBO exposure. These data showed that IE-HBO can potentiate the production and the activity of Prdx6 and consequently mitigate oxidative damages in brain and lungs. The influences of IE-HBO on Prdx6 may form an important basis for its protection against oxygen toxicity.