Abstract
Salivary gland damage caused by ionizing radiation (IR) severely affects the patient quality of life and influences the efficacy of radiotherapy. Most current treatment modalities are palliative, so effective prevention of damage caused by IR is essential. Melatonin (MLT) is an antioxidant that has been reported to prevent IR-induced damage in a range of systems, including the hematopoietic system and gastrointestinal tract. In this study, we explored the effects of MLT on whole-neck irradiation (WNI)-induced salivary gland damage in mice. The results revealed that by protecting the channel protein AQP-5, MLT not only alleviates salivary gland dysfunction and maintains salivary flow rate, but also protects salivary gland structure and inhibits the WNI-induced reduction in mucin production and degree of fibrosis. Compared with WNI-treated mice, in those receiving MLT, we observed a modulation of oxidative stress in salivary glands via its effects on 8-OHdG and SOD2, as well as an inhibition of DNA damage and apoptosis. With respect to its radioprotective mechanism, we found that MLT may alleviate WNI-induced xerostomia partly by regulating RPL18A. In vitro, we demonstrated that MLT has radioprotective effects on salivary gland stem cells (SGSCs). In conclusion, our data this study indicate that MLT can effectively alleviate radiation-induced damage in salivary glands, thereby providing a new candidate for the prevention of WNI-induced xerostomia.