Local and systemic effects of low-dose transtympanic methotrexate: in vivo animal study

To evaluate the safety of low-dose transtympanic methotrexate in a rat model. Experimental animal study. Tertiary training and research hospital. Twenty-four rats were randomly divided into three study groups. Diluted methotrexate solution was administered transtympanically to fill the middle-ear cavity, twice a week in group one and three times a week in group two. Ringer lactate solution was administered transtympanically three times a week in the control group. Local and systemic effects of low-dose transtympanic methotrexate. In the methotrexate groups, middle-ear mucosal oedema was present in all animals. Auditory brainstem response thresholds indicated no inner-ear dysfunction in any group. Liver function and serum haemoglobin levels showed no statistically significant difference in any group. However, liver biopsies from groups one and two showed mild portal hyperaemia. These findings are encouraging, and support further investigation of the topical application of methotrexate in autoimmune hearing diseases, as an alternative or adjunct to transtympanic steroids.