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The salivary glands and oral bacteria play an essential role in the conversion process from nitrate (NO) and nitrite (NO) to nitric oxide (NO) in the human body. NO is, at present, recognized as a multifarious messenger molecule with important vascular and metabolic functions. Besides the endogenous L-arginine pathway, which is catalyzed by complex NO synthases, nitrate in food contributes to the main extrinsic generation of NO through a series of sequential steps (NO-NO-NO pathway). Up to 25% of nitrate in circulation is actively taken up by the salivary glands, and as a result, its concentration in saliva can increase 10- to 20-fold. However, the mechanism has not been clearly illustrated until recently, when sialin was identified as an electrogenic 2NO/H transporter in the plasma membrane of salivary acinar cells. Subsequently, the oral bacterial species located at the posterior part of the tongue reduce nitrate to nitrite, as catalyzed by nitrate reductase enzymes. These bacteria use nitrate and nitrite as final electron acceptors in their respiration and meanwhile help the host to convert nitrate to NO as the first step. This review describes the role of salivary glands and oral bacteria in the metabolism of nitrate and in the maintenance of NO homeostasis. The potential therapeutic applications of oral inorganic nitrate and nitrite are also discussed.

Objective: The aim of this study was to evaluate the influence of thyroid collars on radiation dose during cone beam CT (CBCT) scanning. Methods: Average tissue-absorbed dose for a NewTom 9000 CBCT scanner (Quantitative Radiology, Verona, Italy) was measured using thermoluminescent dosemeter chips in a phantom. The scans were carried out with and without thyroid collars. Effective organ dose and total effective dose were derived using International Commission on Radiological Protection 2007 recommendations. Results: The effective organ doses for the thyroid gland and oesophagus were 31.0 mSv and 2.4 mSv, respectively, during CBCT scanning without a collar around the neck. When the thyroid collars were used loosely around the neck, no effective organ dose reduction was observed. When one thyroid collar was used tightly on the front of the neck, the effective organ dose for the thyroid gland and oesophagus were reduced to 15.9 mSv (48.7% reduction) and 1.4 mSv (41.7% reduction), respectively. Similar organ dose reduction (46.5% and 41.7%) was achieved when CBCT scanning was performed with two collars tightly on the front and back of the neck. However, the differences to the total effective dose were not significant among the scans with and without collars around the neck (p 5 0.775). Conclusions: Thyroid collars can effectively reduce the radiation dose to the thyroid and oesophagus if used appropriately.

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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 (hPGCs). 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-induce xerostomia.

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