Cross-linked hyaluronic acid's effects in rat vestibular and cochlear toxicity model

2.1. Objective and Hypothesis The aim of this study was to investigate the effects of cross-linked hyaluronan molecule in a rat model of vestibulotoxicity and ototoxicity experimentally induced with gentamicin. 2.2. Materials and Methods There were gropus with 7 rats in each. In group A, intratympanic enjection of 13.33 mg / ml of 0.06 ml gentamicin concentration, in grpup B, enjection of 0.06 ml hyaluronic acid autogel, in group C, enjection of 26.66 mg / ml gentamicin + 0.03 ml hyaluronic acid autogel mixture, in group D, enjection of 0.06 ml of saline were administered for consecutive 7 days. All rats were subjected to audiological and vastibular examinations, before the enjections, on days 1, 7 and 10. The rats were sacrificed by applying intracardiac combination of ketamine hydrochloride (50 mg / kg) and xylazine hydrochloride (5 mg / kg) on the 10th day. After sacrification, temporal bones of rats were removed and their cochlea, vestibule, cochlear nerve and spiral ganglion cells were evaluated by light microscope with hematoxylin-eosin, TUNEL and caspase-3 staining methods. 2.3. Results According to the results of the ABR test, gentamicin (A) and combination (C) groups had higher hearing thresholds at all frequencies compared with the other groups. In both groups, statistically significant toxicity was observed at 4, 8, 12, 20 and 32 kHz frequencies beginning from the first 24 hours (p <0.05). Vestibular analysis also showed, the significant adverse effects of gentamicin and combination groups after 24 hours (p <0.05). There were no significant differences between the audiological, vestibular and histological results of the gentamicin and the combination groups (p> 0.05). Histopathological examinations revealed inner and outer hairy cell damage as well as striae vascularis, spiral ganglion, cochlear nerve and vestibular injury in group A (gentamicin) and group C (gentamicin + hyaluronic acid combination). Isolated hyaluronic acid enjection group (B) showed similar results with control saline enjection group (D) except for the temporary effusion effect and hearing loss. Hyaluronic acid did not cause histopathological damage in inner ear. The combination of gentamicin and hyaluronic acid enjection group (C) had a similar effects like isolated gentamicin enjection group (A) in audiological tests, vestibular tests and histopathological examinations. When combination group compared with the gentamicin (A) enjections ototoxicity is not significantly different (p> 0.05). 2.4. Conclusion It was thought that hyaluronic acid molecules did not cause toxic effects on inner ear. When compared with isolated gentamicin, it did not make any significant contribution to ABR thresholds, vestibular balance scores and histopathological findings. Further studies are needed to investigate hyaluronic acid combinations by different methods in order to understand the mechanisms of controlled drug release. Key words: ototoxicity, gentamycin, cross-linked hyaluronic acid, controlled drug release