Dietary Nitrate Supplementation Prevents Radiotherapy-induced Xerostomia

Overview

Journal Elife

Specialty Biology

Date 2021 Sep 28

PMID 34581269

Citations 12

Authors

Xiaoyu Feng

Zhifang Wu

Junji Xu

Yipu Xu

Bin Zhao

Baoxing Pang

Xingmin Qu

Liang Hu

Lei Hu

Zhipeng Fan

Luyuan Jin

Dengsheng Xia

Shimin Chang

Jingsong Wang

Chunmei Zhang

Songlin Wang

Affiliations

Soon will be listed here.

Abstract

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.

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