The impact of tacrolimus on hearing system in rats

The aim of the study is to investigate the effect of tacrolimus – an immunosuppressive agent- on hearing system with distortion product otoacoustic emission (DPOAE) test method. Twenty healthy Spraquey Downey male rats weighing on average 250-350 grams were included to study. Rats were held in cages in the same room and on equal conditions. Background noise level was below 50 dB SPL, the room temperature was 20-22 °C, free water and food were available and light schedule was 12 hours of light and 12 hours of darkness in the room. All rats underwent otoscopic examinations under general anesthesia. Debris and excess ear wax in the external auditory canal of rats were cleaned before the experiment. Intraperitoneal 60 mg/kg of ketamine HCl (Ketalar Ampul, Pfizer, Istanbul) and 6 mg/kg xylazine HCl (Rompun Ampul, Bayer, Istanbul) were used for general anesthesia. There were three groups in the study. The first group was consisted of rats given 1 mg/kg tacrolimus (n=7), the second group included rats given 0,1 mg/kg tacrolimus (n=7) and the third group (n=6) was control group. In our study, rats were given once daily for 30 days at doses determined by tacrolimus gavage. Before the experiment, hearing assessments of all rats were performed and the hearing thresholds of all rats were found to be similar (p> 0,005). The hearing assessments of rats in all groups were studied with DPOAE method on the 30th day of the study. Since the emission results could be different in each ear, otoacoustic emission test was applied to both ears of all rats. DPOAE measurements of all rats were performed prior to administration of tacrolimus. Emissions were obtained in all rats and all were found to be similar as the result of measurements. There were decreases in SNR values after administration of tacrolimus for each group (Table 1, 2, 3). When all groups were compared, the differences between the SNR values obtained from the DPOAE measurements before and after administration of tacrolimus were not statistically significant (Table 4). As the result of our study, DPOAE measurements revealed that there was no statistically significant difference in hearing thresholds between the groups and suggested that tacrolimus at given doses and duration in this study had no toxic effect on hearing system. Key words: ototoxicity, DPOAE, tacrolimus, hearing loss