Ferroptosis, oxidative stress and hearing loss: Mechanistic insights and therapeutic opportunities
Chenyang Yuan,
Tianyu Ma,
Mengting Liu,
Xiaoyun Zeng,
Gongrui Tang,
Yazhi Xing,
Tianhong Zhang
Affiliations
Chenyang Yuan
Department of Otorhinolaryngology Head and Neck surgery, The First Hospital affiliated to Harbin Medical University, Harbin, Heilongjiang, China
Tianyu Ma
Department of Otorhinolaryngology Head and Neck surgery, The First Hospital affiliated to Harbin Medical University, Harbin, Heilongjiang, China
Mengting Liu
Department of Otorhinolaryngology Head and Neck surgery, The First Hospital affiliated to Harbin Medical University, Harbin, Heilongjiang, China
Xiaoyun Zeng
Department of Otorhinolaryngology Head and Neck surgery, The First Hospital affiliated to Harbin Medical University, Harbin, Heilongjiang, China
Gongrui Tang
Department of Otorhinolaryngology Head and Neck surgery, The First Hospital affiliated to Harbin Medical University, Harbin, Heilongjiang, China
Yazhi Xing
Department of Otolaryngology Head and Neck Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai Key Laboratory of Sleep Disordered Breathing, 600 Yishan Rd, Shanghai, 200233, China; Corresponding author.
Tianhong Zhang
Department of Otorhinolaryngology Head and Neck surgery, The First Hospital affiliated to Harbin Medical University, Harbin, Heilongjiang, China; Corresponding author.
Hearing loss, a prevalent sensory impairment, poses significant challenges worldwide. Recent research has shed light on the intricate interplay between ferroptosis, a newly recognized form of regulated cell death characterized by iron-dependent lipid peroxidation, and oxidative stress in the pathogenesis of hearing loss. In this review, we delve into the mechanisms underlying ferroptosis and oxidative stress in various forms of hearing loss, including age-related hearing loss (ARHL), noise-induced hearing loss (NIHL) ototoxic drug-induced hearing loss and genetic hearing loss. We discuss the pivotal role of molecules such as FSP1, ACSL4, LKB1-AMPK, and Nrf2 in modulating these pathways in hearing loss. Furthermore, we explore emerging therapeutic strategies targeting the antioxidant system and ferroptosis, including iron chelators, lipid peroxide inhibitors, and antioxidants, highlighting their potential in mitigating hearing loss progression. By elucidating the molecular mechanisms underlying ferroptosis and oxidative stress, this review offers insights into novel therapeutic avenues for the treatment of hearing loss and underscores the importance of targeting these pathways to preserve auditory function.
