Otoprotective Effect of Nimesulide: Biochemical and Histopathologic Evaluation

Background and Objective: It is known that nimesulide reduces the toxic effects of Non-Steroidal Anti-Inflammatory Drugs (NSAID), eliminating their inhibitory effects on cyclooxygenase-1 (COX-1) enzyme. COX-1 enzyme inhibition is thought to be responsible for aspirin ototoxicity therefore current study aimed to investigate the effect of nimesulide on aspirin ototoxicity in rats. Materials and Methods: Nimesulide 100 mg kg(-1) orally was administered to the nimesulide+aspirin group (NASA) and the same volume of distilled water as solvent was administered to the aspirin group (ASA) and the healthy (HG) group. Aspirin at a dose of 1000 mg kg(-1) was administered orally to the NASA and ASA group one hour after the administration of nimesulide and solvent. This procedure was repeated once a day for 7 days. Then, the animals were euthanized with a high dose of anaesthesia (50 mg kg(-1) thiopental sodium) and their cochlea and cochlear nerve tissues were removed. Results: Malondialdehyde (MDA) level was significantly higher and total glutathione (tGSH) and cyclooxygenase-1 COX-1 levels were significantly lower in the ASA group in which prominent histopathological damage was found in the cochlea and cochlear nerve, compared to the HG and NASA group. The COX-2 level was found to be almost the same in all the g roups. This indicates that aspirin reduces the COX-1 and tGSH levels and increases the MDA level, causing ototoxicity. Conclusion: Aspirin significantly decreased the COX-1 activity in the cochlea and cochlear nerve tissue, compared to the healthy and nimesulide group. Current study concluded that the co-administration of nimesulide and aspirin will increase the therapeutic effect of aspirin and reduces its side-effects.