Erythropoietin Plays a Protective Role in Submandibular Gland Hypofunction Induced by Irradiation

Qilin Liu; Yue Wang; Zhi Cui; Xiaozhou Ma; Haibo Shi; Wei Zhang

doi:10.1016/j.joms.2020.12.001

Erythropoietin Plays a Protective Role in Submandibular Gland Hypofunction Induced by Irradiation

J Oral Maxillofac Surg. 2021 Jun;79(6):1373-1383. doi: 10.1016/j.joms.2020.12.001. Epub 2020 Dec 10.

Authors

Qilin Liu¹, Yue Wang², Zhi Cui³, Xiaozhou Ma⁴, Haibo Shi⁵, Wei Zhang⁶

Affiliations

¹ Associate Chief Surgeon, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun, Jilin Province, China.
² Surgeon, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun, Jilin Province, China; and Department of Oral and Maxillofacial Surgery, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong Province, China.
³ Attending Surgeon, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun, Jilin Province, China.
⁴ Surgeon, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun, Jilin Province, China.
⁵ Resident Surgeon, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun, Jilin Province, China.
⁶ Professor, Chief Surgeon, Head, Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Jilin University, Changchun, Jilin Province, China. Electronic address: wangxr135@hotmail.com.

PMID: 33412114
DOI: 10.1016/j.joms.2020.12.001

Abstract

Purpose: This study aims to explore the radioprotective effects of recombinant human erythropoietin (rhEPO) on rats' submandibular gland hypofunction induced by irradiation (IR).

Materials and methods: Thirty rats were divided into 3 groups: 1) control group, 2) IR group, and 3) IR + rhEPO group. The IR group and IR + rhEPO group received a single dose of 15 Grays (Gy) (0.98 Gy/min), plus, the IR + rhEPO group also received subcutaneous administration of rhEPO at a dose of 3,000 IU/kg body weight 3 days before irradiation and then repeated every 24 hours for the first 2 weeks after irradiation. Immunohistochemistry analysis to erythropoietin receptor was performed to detect the levels of erythropoietin receptor in submandibular glands with or without radiation. Ninety days after irradiation, the salivary flow rates were assessed, and the submandibular gland of every rat was subjected to hematoxylin and eosin staining and immunohistochemical staining with antiaquaporin 5 and anti-proliferating cell nuclear antigen antibodies. Apoptosis was examined by the terminal deoxynucleotidyl transferase biotin-dUDP nick end-labeling assay. In addition, to examine the protective role of rhEPO on human submandibular gland cells, the apoptotic and proliferation rate of cells under a radiation dose of 8 Gy was detected. One-way analysis of variance was carried out to analyze the results of each group, and the P value was set at 0.05.

Results: Erythropoietin receptor was expressed in the submandibular glands at a low level under normal conditions but upregulated after irradiation. rhEPO administration remarkably alleviated gland atrophy, increased salivary flow rates with upregulation of aquaporin-5 compared with the IR group. In addition, fewer apoptotic cells and more proliferative cells were observed in the IR + rhEPO group compared with the IR group, both in vivo and in vitro.

Conclusions: rhEPO administration may be a useful countermeasure to mitigate submandibular gland hypofunction after therapeutic radiation exposure.

MeSH terms

Animals
Apoptosis
Atrophy
Erythropoietin* / pharmacology
Rats
Recombinant Proteins
Submandibular Gland* / pathology

Substances

Recombinant Proteins
Erythropoietin