therefore decided to test whether nitrate could offer protection during neck and head radiotherapy. The nutrient supports the activity and maintenance of the glands, before it is released in the saliva. In the glands, it is ushered into cells thanks to a protein known as sialin. In the body, salivary glands are one of the primary users of a compound known as nitrate, which is commonly found in the diet. Despite this significant impact on quality of life, there is no effective treatment yet for this side effect. This often severely damages the surrounding salivary glands, leading to chronic dry mouth and impairing a patient’s sense of taste, nutrient intake, speech and immune system. Head and neck cancers are commonly treated using radiotherapy, where a beam of high-energy radiation is targeted at the tumour. Dietary nitrate supplementation may provide a novel, safe, and effective way to resolve IR-induced xerostomia. Collectively, nitrate effectively prevented IR-induced xerostomia via the EGFR–AKT–MAPK signaling pathway. 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. 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. 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. 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. Salivary glands, especially the parotid gland, actively uptake dietary nitrate and secrete it into saliva. Management of salivary gland hypofunction caused by irradiation (IR) therapy for head and neck cancer remains lack of effective treatments.
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