Yibing Hu1,2 · Yihuan Zhang1,2 · Shufen Li3  · Yuan Yu1,2 · Jingjing Wang1,2 · Zihan Lou1,2 · Boya Zhang1,2 · Yazhi Xing1,2 · Zhengnong Chen1,2

1 Department of Otolaryngology Head and Neck Surgery, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China 

2 Shanghai Key Laboratory of Sleep Disordered Breathing, Otolaryngology Institute of Shanghai Jiao Tong University, Shanghai 200233, China 

3 Department of Otolaryngology Head and Neck Surgery, First Affiliated Hospital of Nanchang University, Nanchang 330006, China

Abstract

Cisplatin is a widely-used chemotherapeutic agent, but its dose-limiting ototoxicity often results in irreversible hearing loss. The pathogenesis involves oxidative stress, apoptosis, DNA damage, and inflammatory responses, yet effective preventive strategies remain limited. Here, we demonstrate that magnesium hydride (MgH2), a hydrogen-releasing compound, provides robust protection against cisplatin-induced hearing loss. Our results showed that MgH2 protected auditory function and preserved cochlear hair cells in vivo. Furthermore, it significantly attenuated cisplatin-induced oxidative stress and apoptosis in cultured HEI-OC1 (House Ear Institute-Organ of Corti 1) cells and cochlear explants. Notably, MgH2 suppressed NOD-like receptor family pyrin domain containing 3 (NLRP3)-mediated inflammatory cascades, thereby limiting downstream inflammatory damage. These findings revealed that MgH2 alleviated cisplatin-induced hearing loss through integrated antioxidant, anti-inflammatory, and anti-apoptotic pathways, with NLRP3 identified as a critical regulatory molecule. Collectively, our study provides compelling evidence for MgH2 as a potential therapeutic candidate for the prevention of cisplatin-induced hearing loss.

Keywords

Cisplatin-induced ototoxicity; Magnesium hydride; Hearing loss; NLRP3; Infammatory response; Oxidative stress

[SpringerLink]