Dietary nitrate supplementation prevents radiotherapy-induced xerostomia

eLife

Jingsong Wang¹  Chunmei Zhang²  Yipu Xu²  Shimin Chang²  Zhipeng Fan²  Bin Zhao²  Dengsheng Xia²  Xingmin Qu²  Liang Hu²  Lei Hu²  Luyuan Jin²  Junji Xu²  Baoxing Pang²  Zhifang Wu²  Songlin Wang³  Xiaoyu Feng⁴ 

[1] Beijing Laboratory of Oral Health, Capital Medical University, Beijing, China;Biochemistry and Molecular Biology, School of Basic Medical Sciences, Beijing, China;Beijing Laboratory of Oral Health, Capital Medical University, Beijing, China;Salivary Gland Disease Center and Molecular Laboratory for Gene Therapy & Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China;Beijing Laboratory of Oral Health, Capital Medical University, Beijing, China;Salivary Gland Disease Center and Molecular Laboratory for Gene Therapy & Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China;Biochemistry and Molecular Biology, School of Basic Medical Sciences, Beijing, China;Beijing Laboratory of Oral Health, Capital Medical University, Beijing, China;Salivary Gland Disease Center and Molecular Laboratory for Gene Therapy & Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, China;Department of Pediatric Dentistry, Capital Medical University School of Stomatology, Beijing, China;

关键词: miniature pig;    sus scrofa;    minipig;    Other;    Mini pig;   

DOI  :  10.7554/eLife.70710

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY