Investigation of the autotoxic and neurotoxic effect of local diclofenac sodium administration

INTRODUCTION AND OBJECTIVE: Diclofenac Sodium belongs to the non-steroidal anti-inflammatory drugs group and has anti-inflammatory, analgesic and antipyretic effects. With this study, it is aimed to investigate the ototoxic and neurotoxic effect of intratympanic application of diclofenac sodium, which has been shown the cytotoxic effect of it on cholesteatoma tissue.. MATERIALS AND METHODS: Subjects were divided into three groups as saline (negative control), diclofenac sodium (study group), gentamicin (positive control) for ototoxicity evaluation. Ototoxicity was evaluated using distortion product otoacoustic emission (DPOAE), auditory brainstem response (ABR) measurements, and histological analysis. For the evaluation of neurotoxicity, subjects were divided into two groups as saline (negative control) and diclofenac sodium (experimental group). Neurotoxicity was evaluated by functional and histological analysis. RESULTS: In the DPOAE measurements, there was no significant difference between the three groups in preoperatiferative measurements (p0.05). While there was a significant difference between the three groups (p<0.05) in the postoperative 3rd day measurement. There was no significant difference between the diclofenac and gentamicin groups in the paired comparisons in the posthoc analysis (p0.05). In the postoperative 28th day comparison, there was a significant difference between the three groups (p <0.05). In the ABR measurements, there was a significant increase in threshold in the diclofenac and gentamicin groups (p <0.05) However no significant change was observed in the saline group (p0.05). In histological analysis of ototoxicity, cytoplasmic vacuolizations, cellular degeneration, and degree of dilatation were found to be higher in the gentamicin group compared to the diclofenac sodium group (p <0.05). A significant difference was found between each group in the apoptotic cell and neural degeneration scores (p <0.05). In the histological analysis of neurotoxicity, there was no significant difference between the two groups (p0.05). CONCLUSION: Diclofenac sodium has been shown to have an ototoxic effect in its local application into the middle ear, but it has not a neurotoxic effect. This molecule, which has a known cytotoxic effect on cholesteatoma tissue, can be considered to be used as supportive treatment, especially in advanced cholesteatoma cases without usable hearing or whose hearing may be sacrificed. Keywords: Diclofenac Sodium; Distortion Product Otoacoustic Emission; Auditory Brainstem Response; Neurotoxicity; Ototoxicity