Evaluation of ototoxicity of intratympanic administration of Methotrexate in rats

Objective: Methotrexate is a dihydrofolate reductase enzyme inhibitor with very high selectivity, and it is an antiproliferative folic acid antagonist used for the treatment of autoimmune diseases. In this study, our objective was to evaluate the effect of intratympanic Methotrexate application in the inner ear.

Methods: This study was planned as an animal study. This study performed in a tertiary referral center. 24 healthy female rats were used in our study. They were separated into three groups. 0.2 cc intratympanic saline was applied to both ears of Group 1. Paracentesis was applied to the tympanic membrane in both ears of Group 2. 0.2 cc intratympanic Methotrexate was applied to both ears of Group 3. At the beginning of the study, Distortion-product otoacoustic emissions (DPOAE) and Auditory brainstem response (ABR) of all rats were measured and then again on the 5th, 10th and 15th day. Histologic examinations of all groups were compared.

Results: There was not any significant difference between basal DPOAE and ABR measurement values of the groups and the results were measured again on the 5th, 10th and 15th day (p > 0.05). There was no difference between the groups in terms of histology.

Conclusion: The intratympanic Methotrexate injection does not have any ototoxic effect on inner ear. We assume that intratympanic Methotrexate could be used safely on inner ear diseases in which steroid treatment is contraindicated or not effective.