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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)\u2013protein kinase B (AKT)\u2013mitogen-activated protein kinase (MAPK) signaling pathway in irradiated parotid gland tissue. Collectively, nitrate effectively prevented IR-induced xerostomia via the EGFR\u2013AKT\u2013MAPK signaling pathway. Dietary nitrate supplementation may provide a novel, safe, and effective way to resolve IR-induced xerostomia.<\/jats:p>","DOI":"10.7554\/elife.70710","type":"journal-article","created":{"date-parts":[[2021,9,28]],"date-time":"2021-09-28T08:00:38Z","timestamp":1632816038000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.70710","source":"Crossref","is-referenced-by-count":39,"title":["Dietary nitrate supplementation prevents radiotherapy-induced xerostomia"],"prefix":"10.7554","volume":"10","author":[{"given":"Xiaoyu","family":"Feng","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Beijing Laboratory of Oral Health, Capital Medical University","place":["Beijing, China"]},{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Salivary Gland Disease Center and Molecular Laboratory for Gene Therapy & Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration 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