TY - JOUR TI - Dietary nitrate supplementation prevents radiotherapy-induced xerostomia AU - Feng, Xiaoyu AU - Wu, Zhifang AU - Xu, Junji AU - Xu, Yipu AU - Zhao, Bin AU - Pang, Baoxing AU - Qu, Xingmin AU - Hu, Liang AU - Hu, Lei AU - Fan, Zhipeng AU - Jin, Luyuan AU - Xia, Dengsheng AU - Chang, Shimin AU - Wang, Jingsong AU - Zhang, Chunmei AU - Wang, Songlin A2 - El-Deiry, Wafik S A2 - Bunz, Fred A2 - Zheng, Changyu VL - 10 PY - 2021 DA - 2021/09/28 SP - e70710 C1 - eLife 2021;10:e70710 DO - 10.7554/eLife.70710 UR - https://doi.org/10.7554/eLife.70710 AB - Management of salivary gland hypofunction caused by irradiation (IR) therapy for head and neck cancer remains lack of effective treatments. Salivary glands, especially the parotid gland, actively uptake dietary nitrate and secrete it into saliva. Here, we investigated the effect of dietary nitrate on the prevention and treatment of IR-induced parotid gland hypofunction in miniature pigs, and elucidated the underlying mechanism in human parotid gland cells. We found that nitrate administration prevented IR-induced parotid gland damage in a dose-dependent manner, by maintaining the function of irradiated parotid gland tissue. Nitrate could increase sialin expression, a nitrate transporter expressed in the parotid gland, making the nitrate-sialin feedback loop that facilitates nitrate influx into cells for maintaining cell proliferation and inhibiting apoptosis. Furthermore, nitrate enhanced cell proliferation via the epidermal growth factor receptor (EGFR)–protein kinase B (AKT)–mitogen-activated protein kinase (MAPK) signaling pathway in irradiated parotid gland tissue. Collectively, nitrate effectively prevented IR-induced xerostomia via the EGFR–AKT–MAPK signaling pathway. Dietary nitrate supplementation may provide a novel, safe, and effective way to resolve IR-induced xerostomia. KW - miniature pig KW - sus scrofa KW - minipig JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -