1. Academic Validation
  2. Citicoline Protects Auditory Hair Cells Against Neomycin-Induced Damage

Citicoline Protects Auditory Hair Cells Against Neomycin-Induced Damage

  • Front Cell Dev Biol. 2020 Aug 31:8:712. doi: 10.3389/fcell.2020.00712.
Zhenhua Zhong 1 2 Xiaolong Fu 3 He Li 4 Jie Chen 1 Maohua Wang 5 Song Gao 6 Liyan Zhang 3 Cheng Cheng 1 Yuan Zhang 3 Peipei Li 7 Shasha Zhang 3 Xiaoyun Qian 1 Yilai Shu 8 Renjie Chai 3 9 10 11 Xia Gao 1
Affiliations

Affiliations

  • 1 Jiangsu Provincial Key Medical Discipline (Laboratory), Department of Otolaryngology Head and Neck Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China.
  • 2 Department of Otolaryngology, Head and Neck Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.
  • 3 MOE Key Laboratory for Developmental Genes and Human Disease, Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research, Institute of Life Sciences, Southeast University, Nanjing, China.
  • 4 Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 5 Department of Otolaryngology, Head and Neck Surgery, Xiangya School of Medicine, Central South University, Changsha, China.
  • 6 Department of Otolaryngology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, China.
  • 7 School of Life Sciences, Shandong University, Jinan, China.
  • 8 ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Institute of Biomedical Sciences, NHC Key Laboratory of Hearing Medicine, Fudan University, Shanghai, China.
  • 9 Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China.
  • 10 Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing, China.
  • 11 Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, China.
Abstract

Aminoglycoside-induced hair cell (HC) loss is one of the most important causes of hearing loss. After entering the inner ear, aminoglycosides induce the production of high levels of Reactive Oxygen Species (ROS) that subsequently activate Apoptosis in HCs. Citicoline, a nucleoside derivative, plays a therapeutic role in central nervous system injury and in neurodegenerative disease models, including addictive disorders, stroke, head trauma, and cognitive impairment in the elderly, and has been widely used in the clinic as an FDA approved drug. However, its effect on auditory HCs remains unknown. Here, we used HC-like HEI-OC-1 cells and whole organ explant cultured mouse cochleae to explore the effect of citicoline on aminoglycoside-induced HC damage. Consistent with previous reports, both ROS levels and Apoptosis were significantly increased in neomycin-induced cochlear HCs and HEI-OC-1 cells compared to undamaged controls. Interestingly, we found that co-treatment with citicoline significantly protected against neomycin-induced HC loss in both HEI-OC-1 cells and whole organ explant cultured cochleae. Furthermore, we demonstrated that citicoline could significantly reduce neomycin-induced mitochondrial dysfunction and inhibit neomycin-induced ROS accumulation and subsequent Apoptosis. Thus, we conclude that citicoline can protect against neomycin-induced HC loss by inhibiting ROS aggregation and thus preventing Apoptosis in HCs, and this suggests that citicoline might serve as a potential therapeutic drug in the clinic to protect HCs.

Keywords

aminoglycosides; apoptosis; citicoline; hair cell; reactive oxygen species.

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