Therapeutic Potential of MgH₂ in Mitigating Cisplatin-Induced Hearing Loss

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.