Exploring the efficacy of (R)-PFI-2 hydrochloride in mitigating noise-induced hearing loss by targeting NLRP3 inflammasome and NF-κB pathway to reduce inner ear inflammation

作者：Dawei Ren, Xuemin Chen, Hongdong Liu, Meng-Hua Li, Liting Zheng, Yong Pan, Mohe Huang, Xi Shi, Yice Xu, Shujin Chen, Yan Zhang, Wei Zhu · 发表于：Journal of Otology · 年份：2024 · DOI：10.1016/j.joto.2024.07.008 · 被引用次数：4 · 研究领域：Inflammasome and immune disorders、Pediatric health and respiratory diseases、IL-33, ST2, and ILC Pathways

Noise-induced hearing loss (NIHL) is primarily driven by inflammatory processes within the cochlea, where noise exposure triggers the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, leading to an inflammatory cascade. The interaction between increased NLRP3 expression and NF-κB activity can further amplify cochlear inflammation. Our findings reveal that (R)-PFI-2 hydrochloride, a selective inhibitor of the SETD7 enzyme, effectively inhibits the activation of the cochlear NF-κB pathway, suppresses the release of pro-inflammatory factors, and prevents inflammasome assembly. This intervention disrupts the perpetuating cycle of inflammation, thereby alleviating damage to cochlear hair cells attributed to acoustic trauma. Consequently, (R)-PFI-2 hydrochloride emerges as a promising pharmacological candidate for NIHL, targeting and moderating the excessive immune and inflammatory responses implicated in the pathology of hearing loss.