Considering the protective effect of exendin-4 against oxidative stress in spiral ganglion neurons

作者全名："Wu, Hongxia; Ou, Yangxi; Wang, Siji; Yu, Fenghui; Fan, Xiaoxia; Kang, Houyong; Chen, Tao"

作者地址："[Wu, Hongxia; Ou, Yangxi; Wang, Siji; Yu, Fenghui; Fan, Xiaoxia; Kang, Houyong; Chen, Tao] Chongqing Med Chongqing, Affiliated Hosp 1, Dept Otorhinolaryngol, Chongqing, Peoples R China; [Kang, Houyong] Chongqing Med Univ, Affiliated Hosp 1, Dept Otorhinolaryngol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Kang, HY; Chen, T (通讯作者)，Chongqing Med Chongqing, Affiliated Hosp 1, Dept Otorhinolaryngol, Chongqing, Peoples R China.; Kang, HY (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Otorhinolaryngol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：IRANIAN JOURNAL OF BASIC MEDICAL SCIENCES

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001094009200006

JCR分区：Q3

影响因子：2.1

年份：2023

卷号：26

期号：12

开始页：1423

结束页：1430

文献类型：Article

关键词：Exenatide; Hearing loss; Kanamycin; Mice; Oxidative damage; Spiral ganglio

摘要："Objective(s): The protection of spiral ganglion neurons (SGNs) is crucial for hearing loss. Exendin-4 has been shown to have neuroprotective effects in several neurological disorders. Therefore, this study aimed to investigate the effect of the glucagon-like protein-1 receptor (GLP-1R) agonist exendin-4 on kanamycin-induced injury in mouse SGNs in vitro.Materials and Methods: In this study, GLP-1R expression in SGNs was verified by immunofluorescence and immunohistochemical staining. In vitro-cultured SGNs and the organ of Corti were exposed to kanamycin with or without exendin-4 treatment. The cell survival rate was measured using the cell counting kit-8 assay, and the damage to auditory nerve fibers (ANF) projecting radially from the SGNs was evaluated using immunofluorescence staining. Reactive oxygen species (ROS) content was determined by flow cytometry, and glutathione peroxidase (GSH-Px) content, superoxide dismutase (SOD) activity, and malondialdehyde (MDA) content were determined by spectrophotometry. Protein expression of nuclear factor erythroid-2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) was detected using western blotting.Results: GLP-1R was expressed in SGNs. Treatment with 1 mM kanamycin for 24 hr induced SGN damage. Exendin-4 (100 nM) had a protective effect against kanamycin-induced SGN cell injury, improved cell survival rate, reduced nerve fiber injury, increased SOD activity and GSH-Px level, and reduced MDA and ROS contents. The Nrf2/HO-1 pathway was activated.Conclusion: Exendin-4 alleviates oxidative damage and exerts neuroprotective effects in kanamycin-induced SGN injury through the Nrf2/HO-1 signaling pathway. Exendin-4 has the potential to prevent or treat hearing loss due to SGN damage."

基金机构："National Natural Science Foundation of China (NSFC) [81900946]; Technology Innovation and Application Development Special Key Project [CSTC2021jscx-gksb-N0011]; Program for Youth Innovation in Future Medicine, Chongqing Medical University"

基金资助正文："This study was funded by The National Natural Science Foundation of China (NSFC) (No:81900946) ; Chongqing. Technology Innovation and Application Development Special Key Project (No:CSTC2021jscx-gksb-N0011) ; and Program for Youth Innovation in Future Medicine, Chongqing Medical University."