Hyperoxia reduces salivary secretion by inducing oxidative stress in mice

•Hyperoxia (75% oxygen for 5 days) reduced salivary secretion in mice.•Enlarged mucous acini were seen in the hyperoxia-exposed salivary glands.•Increased TUNEL-positive cells in the hyperoxia-exposed salivary glands.•Hyperoxia increased HO-1, SOD-1, and SOD-2 mRNA expression in the salivary glands.•The submandibular gland might be highly sensitive to oxidative stress. Objective: The aim of this study was to determine the effects of prolonged hyperoxia on salivary glands and salivary secretion in mice. Design: Male C57BL/6 J mice were kept in a 75% oxygen chamber (hyperoxia group) or a 21% oxygen chamber for 5 days. We measured the secretion volume, protein concentration, and amylase activity of saliva after the injection of pilocarpine. In addition, we evaluated the histological changes induced in the submandibular glands using hematoxylin and eosin and Alcian blue staining and assessed apoptotic changes using the TdT-mediated dUTP nick end labeling (TUNEL) assay. We also compared the submandibular gland expression levels of heme oxygenase-1 (HO-1), superoxide dismutase (SOD)-1, and SOD-2 using the real-time polymerase chain reaction. Results: In the hyperoxia group, salivary secretion was significantly inhibited at 5 and 10 min after the injection of pilocarpine, and the total salivary secretion volume was significantly decreased. The salivary protein concentration and amylase activity were also significantly higher in the hyperoxia group. In the histological examinations, enlargement of the mucous acini and the accumulation of mucins were observed in the submandibular region in the hyperoxia group, and the number of TUNEL-positive cells was also significantly increased in the hyperoxia group. Moreover, the expression levels of HO-1, SOD-1, and SOD-2 were significantly higher in the hyperoxia group. Conclusion: Our results suggest that hyperoxia reduces salivary secretion, and oxidative stress reactions might be involved in this.