title: Inhibition of cyclooxygenase-2 by NS398 attenuates noise-induced hearing loss in mice.
abstract: Noise-induced hearing loss (NIHL) is an important occupational disorder. However, the molecular mechanisms underlying NIHL have not been fully clarified; therefore, the condition lacks effective therapeutic methods. Cyclooxygenase-2 (Cox-2) is an inducible enzyme involved in the synthesis of prostaglandins, and has been implicated in many pathophysiological events, such as oxidative stress and inflammation. In this study, we investigated the possible role of Cox-2 in the mechanisms of NIHL and the therapeutic effect of the Cox-2 inhibitor NS398 on NIHL using a mouse model. We demonstrated that Cox-2 is constitutively expressed in the mouse cochlea, and its expression could be dramatically up-regulated by high levels of noise exposure. Furthermore, we demonstrated that pre-treatment with the Cox-2 inhibitor NS398 could inhibit Cox-2 expression during noise overstimulation; and could attenuate noise-induced hearing loss and hair cell damage. Our results suggest that Cox-2 is involved in the pathogenesis of NIHL; and pharmacological inhibition of Cox-2 has considerable therapeutic potential in NIHL.
authors.affiliation: Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Otolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology, Emory University School of Medicine, 615 Michael Street, Atlanta, GA 30322-3030, USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Otolaryngology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, PR China.
authors.forename: Wenxue
authors.initials: W
authors.lastname: Tang
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D034381:Hearing Loss / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D051379:Mice; D009578:Nitrobenzenes / Q000494:pharmacology*; D009622:Noise / Q000009:adverse effects*; D013449:Sulfonamides / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2