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Biochem Biophys Res Commun. 2018 Feb 26;497(1):272-278. doi: 10.1016/j.bbrc.2018.02.068. Epub 2018 Feb 9.

Dietary nitrate protects submandibular gland from hyposalivation in ovariectomized rats via suppressing cell apoptosis.

Author information

1
Molecular Laboratory for Gene Therapy & Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Tian Tan Xi Li No.4, Beijing 100050, China.
2
Molecular Laboratory for Gene Therapy & Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Tian Tan Xi Li No.4, Beijing 100050, China; Department of Oral & Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Shandong Province, China.
3
Molecular Laboratory for Gene Therapy & Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Tian Tan Xi Li No.4, Beijing 100050, China; Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, You An Men Wai Xi TouTiao No.10, Beijing 100069, China.
4
Molecular Laboratory for Gene Therapy & Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Tian Tan Xi Li No.4, Beijing 100050, China; Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, You An Men Wai Xi TouTiao No.10, Beijing 100069, China. Electronic address: slwang@ccmu.edu.cn.

Abstract

Xerostomia, a major oral symptom of menopause, is a subjective feeling of dry mouth associated with oral pain and difficulties in deglutition and speech, which significantly reduces patient's quality of life. Dietary nitrate, which can be converted to nitric oxide, has multiple physiological functions in the body, including antioxidant activity and vasodilatation; however, its protective effect against xerostomia remains poorly understood. The present study aimed to evaluate the effects of dietary nitrate on estrogen deficiency-induced xerostomia. We established an ovariectomized (OVX) rat model, which included five groups: sham-operated, OVX, OVX + 0.4 mM nitrate, OVX + 2 mM nitrate, and OVX + 4 mM nitrate (n = 6). After ovariectomy, animals in the nitrate treatment groups received appropriate amounts of sodium nitrate dissolved in distilled water for 3 months. The results showed that nitrate treatment reduced body weight and water intake, and increased serum nitrate and nitrite levels. Furthermore, nitrate uptake increased saliva secretion as evidenced by saliva flow rates and aquaporin 5 expression, and alleviated histological lesions as evidenced by reduction of the fibrotic area and cell atrophy in the salivary glands. Although protective effects of nitrate against estrogen deficiency-induced xerostomia were observed at all doses, treatment with 2 mM nitrate was more effective than that with 0.4 mM and 4 mM nitrate. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase-3 expression analyses showed that nitrate also protected cells from apoptosis, possibly through upregulation of Cu-Zn superoxide dismutase (Cu-Zn SOD) known to inhibit oxidative stress-related apoptosis. Our findings indicate that nitrate could improve functional activity of the salivary glands in OVX rats by suppressing apoptosis and upregulating Cu-Zn SOD expression, suggesting that dietary nitrate may potentially prevent hyposalivation in menopausal women.

KEYWORDS:

Apoptosis; Hyposalivation; Nitrate; Salivary glands; Xerostomia

PMID:
29432741
DOI:
10.1016/j.bbrc.2018.02.068
[Indexed for MEDLINE]

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