Dietary nitrate supplementation prevents radiotherapy-induced xerostomia

作者：Xiaoyu Feng, Zhifang Wu, Junji Xu, Yipu Xu, Bin Zhao, Baoxing Pang, Xingmin Qu, Hu L, Lei Hu, Zhipeng Fan, Luyuan Jin, Dengsheng Xia, Shi‐Min Chang, Jingsong Wang, Chunmei Zhang, Songlin Wang · 发表于：eLife · 年份：2021 · DOI：10.7554/elife.70710 · 被引用次数：41 · 研究领域：Salivary Gland Disorders and Functions、Cancer, Hypoxia, and Metabolism、Neurological Disease Mechanisms and Treatments

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.