Effects of Cross-linked Hyaluronic Acid in a Rat Model of Vestibular and Cochlear Toxicity

Turk Arch Otorhinolaryngol. 2023 Sep;61(3):124-133. doi: 10.4274/tao.2023.2023-5-14. Epub 2023 Nov 14.


Objective: To investigate the effects of cross-linked hyaluronic acid (CLHA) in an experimental model of vestibulotoxicity and cochleotoxicity.

Methods: Twenty-eight female Wistar albino rats (200-250 g) were divided into four groups. Group A received 0.06 mL of 13.33 mg/mL gentamicin, Group B received 0.06 mL of CLHA, Group C received 0.03 mL of 26.66 mg/mL gentamicin and 0.03 mL CLHA, and Group D received 0.06 mL of 0.09% saline. All groups underwent auditory brainstem response testing at 4-32 kHz, signal-to-noise ratio of distortion product otoacoustic emission measurements at 1.5-8 kHz and vestibular tests on days 0,1,7,10. The rats were sacrificed, and their labyrinths were histologically assessed and scored.

Results: The hearing thresholds of Groups A and C were similar and significantly higher than those of the other groups at all frequencies, beginning from day 1. The vestibular and histological scores of Groups A and C were similar and significantly higher than those of the other groups from day 1. The audiological results, vestibular scores, and histological scores of Groups B and D were similar, except for a temporary middle ear effusion and hearing threshold shift in Group B. No significant deterioration was observed in the audiological, vestibular, and histological analyses of Groups B and D.

Conclusion: That both Group A and Group C similarly showed worsening audiological, vestibular, and histological tests suggests that CLHA did not alter the pharmacokinetics and histologic results of gentamicin.

Keywords: Gentamicin; animal research; audiology; drug-related ototoxicity; hearing loss; hyaluronan; vestibular function tests.