Topical rifamycin aplication in rat model investigation of ototoxic and middle ear mucosa effects experimental study

Purpose: The aim of this study is to investigate the use of topical rifamycin in chronic otitis media model about (1) the possible histopathological effects on the rat middle ear mucosa (2) the potential negative effects on hearing in functional way. It is targeted with this study to contribute literature about whether rifampicin applied as ear drops is reliable. Materials and Methods: This experimental study was conducted on 30 rats, in Baskent University Faculty of Medicine Experimental Animal Research Laboratory. The rats were divided into 3 groups according to the duration of treatment. After perforation of the both tympanic membrane rifamycin 3x2 drops per day was applied to the right ear. While the left ear did not receive any treatment. Group I 1 week, group II 2 weeks, group III 3 weeks of treatment were given. Before and after treatment in both ears, the distortion product otoacoustic emissions (DPOAE) measurements, is performed considering signal to noise ratio (SNR). After the treatment rats were decapitated and middle ear mucosa was dissected and was delivered blind to the pathology. Results: In the treated ears in group I at 2 kHz significant increase in SNR (p = 0.022) was observed relative to upon perforation of the ear; In the control ear in group I showed a significant increase in 6 kHz. After perforation and post-treatment SNR values compared to between right and left ears at all frequencies statistically no significant difference was observed (p> 0.05). SNR values compared between groups all frequencies before and after treatment showed no significant difference (p >0.017; Bonferroni correction). Histopathologically between rifampicin administered right ears and control left ears no significant differences were found in terms of; inflammation, fibrosis, foreign body reaction, vascular proliferation and pigment containing histiocytes (p> 0.05). However, in the right ear between groups, pigment containing histiocytes were significantly higher in the group I and II (p = 0.018). Conclusions: I) This study showed that topical rifampicin application in rats have no significant effect on middle ear mucosa in terms of inflammation, fibrosis, foreign body reactions, vascular proliferation and pigment containing histiocytes, compared to control ears. In treatment given ear increase in the number of histiocytes containing pigments in the first two weeks has been observed, but in the third week this situation improves. II) Whereas topical application of rifamycin in rats, caused no is significantly lower SNR value, it was concluded that between 2-6 kHz no ototoxic effects on hearing exists. III) based on these findings, it was concluded to be in chronic otitis model application of topical rifamycin even for 3 weeks is safe for the ototoxicity and middle ear mucosa. IV) It is thought that these results should be supported by forward experimental and clinical studies evaluating the inner ear histopathology and high frequency hearing thresholds. Keywords: Rat, Ototoxicity, Rifamycin, Middle Ear, topical.