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
Dawei Ren1
Xuemin Chen2
Hongdong Liu3
Menghua Li4
Liting Zheng4
Pan Yong4
Mohe Huang5
Xi Shi6
Yice Xu7
Shujin Chen8
Yan Zhang1
Wei Zhu1
1.Department of Otorhinolaryngology,the First Hospital of Jilin University,Changchun,130021,Jilin,China2.Department of Otorhinolaryngology,No.971 Hospital of People's Liberation Army Navy,Qingdao,266000,Shandong Province,China;Senior Department of Otolaryngology-Head & Neck Surgery,Chinese PLA General Hospital,National Clinical Research Center for Otolaryngologic Diseases,State Key Lab of Hearing Science,Ministry of Education,Beijing Key Lab of Hearing Impairment Prevention and Treatment,Beijing,100083,China3.Senior Department of Otolaryngology-Head & Neck Surgery,Chinese PLA General Hospital,National Clinical Research Center for Otolaryngologic Diseases,State Key Lab of Hearing Science,Ministry of Education,Beijing Key Lab of Hearing Impairment Prevention and Treatment,Beijing,100083,China4.Artificial Auditory Laboratory of Jiangsu Province,Xuzhou Medical University,Xuzhou,221000,Jiangsu,China5.Key Laboratory of Tropical Biological Resources of Ministry of Education,School of Pharmaceutical Sciences,Hainan University,Haikou,570228,Hainan Provine,China;Song Li's Academician Workstation of Hainan University,School of Pharmaceutical Sciences,Yazhou Bay,Sanya,572000,Hainan Provine,China6.Artificial Auditory Laboratory of Jiangsu Province,Xuzhou Medical University,Xuzhou,221000,Jiangsu,China;Key Laboratory of Tropical Biological Resources of Ministry of Education,School of Pharmaceutical Sciences,Hainan University,Haikou,570228,Hainan Provine,China;Song Li's Academician Workstation of Hainan University,School of Pharmaceutical Sciences,Yazhou Bay,Sanya,572000,Hainan Provine,China7.Department of Otolaryngology-Head and Neck Surgery,The Central Hospital of Xiaogan,Xiaogan,432000,Hubei,China8.ENT Department,The People's Hospital of Rongchang District,Chongqing 402460,China
摘要：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 in-flammatory 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.
机标关键词：reducenlrp3pathwaylossefficacyexploringhearinghydrochloride
论文发表日期：2024-12-30
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：7( 200-206 )
英文信息