Assessment of the Potential Ototoxicity of High-Dose Celecoxib, a Selective Cyclooxygenase-2 Inhibitor, in Rats

Objective To evaluate the potential ototoxicity of high-dose celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor. Study Design Prospective animal study. Setting Laboratory. Methods Twenty adult male Sprague Dawley rats were divided into 2 groups for hearing and tinnitus tests, respectively. The auditory brain-stem response (ABR) and the gap prepulse inhibition of acoustic startle (GPIAS) were used as indicators of hearing loss and tinnitus, respectively, and were measured before and at 2, 4, 6, 8, 12, 24, and 48 hours after administration of celecoxib (2 g/kg) via gavage. Results ABR threshold and wave III latencies did not increase significantly at any frequency following celecoxib administration, at any time point (P > .05). GPIAS remained below 30% after celecoxib, from a baseline of 20.03% ± 3.62%; no change was significant. Conclusion High-dose celecoxib (2 g/kg), a selective COX-2 inhibitor, did not cause hearing loss or tinnitus in Sprague Dawley rats within 48 hours of administration. Further studies are needed to explore the roles played by COX-related mechanisms when nonselective COX inhibitors induce ototoxicity.

[1]  Yan-jun Lv,et al.  Clopidogrel plus aspirin versus aspirin alone for preventing early neurological deterioration in patients with acute ischemic stroke , 2015, Journal of Clinical Neuroscience.

[2]  Jun Ma,et al.  Changes in the Numbers of Ribbon Synapses and Expression of RIBEYE in Salicylate-Induced Tinnitus , 2014, Cellular Physiology and Biochemistry.

[3]  N. Brereton,et al.  A cost-effectiveness analysis of celecoxib compared with diclofenac in the treatment of pain in osteoarthritis (OA) within the Swedish health system using an adaptation of the NICE OA model , 2014, Journal of medical economics.

[4]  Y. Yamaoka,et al.  Role of Preferential Cyclooxygenase-2 Inhibition by Meloxicam in Ischemia/Reperfusion Injury of the Rat Liver , 2014, European Surgical Research.

[5]  R. Salvi,et al.  Review of salicylate-induced hearing loss, neurotoxicity, tinnitus and neuropathophysiology , 2014, Acta otorhinolaryngologica Italica : organo ufficiale della Societa italiana di otorinolaringologia e chirurgia cervico-facciale.

[6]  A. Conney,et al.  A triple combination of atorvastatin, celecoxib and tipifarnib strongly inhibits pancreatic cancer cells and xenograft pancreatic tumors , 2014, International journal of oncology.

[7]  M. F. Coronel,et al.  Progesterone reduces the expression of spinal cyclooxygenase‐2 and inducible nitric oxide synthase and prevents allodynia in a rat model of central neuropathic pain , 2014, European journal of pain.

[8]  Angel Lanas,et al.  Aspirin, cyclooxygenase inhibition and colorectal cancer. , 2014, World journal of gastrointestinal pharmacology and therapeutics.

[9]  J. Chen,et al.  Expression of Immediate-Early Genes in the Inferior Colliculus and Auditory Cortex in Salicylate-Induced Tinnitus in Rat , 2014, European journal of histochemistry : EJH.

[10]  W. Niu,et al.  The Association of Four Common Polymorphisms from Four Candidate Genes (COX-1, COX-2, ITGA2B, ITGA2) with Aspirin Insensitivity: A Meta-Analysis , 2013, PloS one.

[11]  R. Moore,et al.  Single dose oral celecoxib for acute postoperative pain in adults. , 2013, The Cochrane database of systematic reviews.

[12]  M. Björkholm,et al.  Telomerase reverse transcriptase inhibition stimulates cyclooxygenase 2 expression in cancer cells and synergizes with celecoxib to exert anti-cancer effects , 2013, British Journal of Cancer.

[13]  Y. Chan,et al.  Effects of C-phycocyanin and Spirulina on Salicylate-Induced Tinnitus, Expression of NMDA Receptor and Inflammatory Genes , 2013, PloS one.

[14]  Nimisha P. Patel,et al.  Resveratrol Decreases Noise-Induced Cyclooxygenase-2 Expression in the Rat Cochlea , 2013, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

[15]  R. Salvi,et al.  Salicylate-induced cochlear impairments, cortical hyperactivity and re-tuning, and tinnitus , 2013, Hearing Research.

[16]  J. Mehta,et al.  Aspirin suppresses cardiac fibroblast proliferation and collagen formation through downregulation of angiotensin type 1 receptor transcription. , 2012, Toxicology and applied pharmacology.

[17]  M. Hyppolito,et al.  Spontaneous reversibility of damage to outer hair cells after sodium salicylate induced ototoxicity. , 2011, The Journal of laryngology and otology.

[18]  M. Lordkipanidzé,et al.  Heterogeneity in platelet cyclooxygenase inhibition by aspirin in coronary artery disease. , 2011, International journal of cardiology.

[19]  Xiaorui Shi,et al.  Fibro-Vascular Coupling in the Control of Cochlear Blood Flow , 2011, PloS one.

[20]  Ming-Fu Wang,et al.  Expression of COX‐2 and NMDA receptor genes at the cochlea and midbrain in salicylate‐induced tinnitus , 2011, The Laryngoscope.

[21]  E. Nwose,et al.  Whole blood viscosity issues VI: Association with blood salicylate level and gastrointestinal bleeding , 2010, North American journal of medical sciences.

[22]  Jiwon Chang,et al.  Expression of Insulin-like Growth Factors in a Mouse Model of Salicylate Ototoxicity , 2010, Clinical and experimental otorhinolaryngology.

[23]  L. Pezard,et al.  Neural changes in the auditory cortex of awake guinea pigs after two tinnitus inducers: salicylate and acoustic trauma , 2010, Neuroscience.

[24]  I. Schmidtmann,et al.  Noise exposure alters cyclooxygenase 1 (COX-1) and 5-lipoxygenase (5-LO) expression in the guinea pig cochlea. , 2010, Acta oto-laryngologica.

[25]  E. Lobarinas,et al.  Salicylate increases the gain of the central auditory system , 2009, Neuroscience.

[26]  Jae Heun Lee,et al.  The obligatory role of COX-2 expression for induction of HO-1 in ischemic preconditioned rat brain. , 2008, Biochemical and biophysical research communications.

[27]  G. Scadding,et al.  COX-1, and not COX-2 activity, regulates airway function: relevance to aspirin-sensitive asthma , 2008, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[28]  A. Staffieri,et al.  The Discovery of Salicylate Ototoxicity , 2007, Audiology and Neurotology.

[29]  M. Kowalski,et al.  Alternative splicing of cyclooxygenase‐1 gene: altered expression in leucocytes from patients with bronchial asthma and association with aspirin‐induced 15‐HETE release , 2007, Allergy.

[30]  Edgar Erdfelder,et al.  G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences , 2007, Behavior research methods.

[31]  Edward Lobarinas,et al.  Salicylate induced tinnitus: Behavioral measures and neural activity in auditory cortex of awake rats , 2007, Hearing Research.

[32]  H. Jung,et al.  Expressions of cyclooxygenase 1 and 2 in endotoxin-induced otitis media with effusion in the rat. , 2007, International journal of pediatric otorhinolaryngology.

[33]  U. Peleg,et al.  Salicylate Ototoxicity and its Implications for Cochlear Microphonic Potential Generation , 2007, Journal of basic and clinical physiology and pharmacology.

[34]  W. Mann,et al.  COX-2 expression in the guinea pig cochlea is partly altered by moderate sound exposure , 2006, Neuroscience Letters.

[35]  D. Robertson,et al.  [The electro-physiological change of guinea pig cochlea caused by intracochlear perfusion of sodium salicylate]. , 2003, Lin chuang er bi yan hou ke za zhi = Journal of clinical otorhinolaryngology.

[36]  T. Jung,et al.  Effect of leukotriene inhibitor on otoacoustic emissions in salicylate ototoxicity. , 1996, The American journal of otology.

[37]  S. Miller,et al.  Effect of leukotriene inhibitor on cochlear blood flow in salicylate ototoxicity. , 1995, Acta oto-laryngologica.

[38]  P. Stypulkowski Mechanisms of salicylate ototoxicity , 1990, Hearing Research.