Comparative Ototoxic Potential of Hyaluronic Acid and Methylcellulose

Abstract

In experimental animal studies, exogenous hyaluronan (HA) has been shown to exert beneficial effects on the healing of tympanic membrane perforation. As any other exogenous substance, HA may prove potentially toxic, by filling the middle ear cavity, to the sensory cells of the organ of Corti. Electrophysiological (ABR) and morphological studies were carried out in the rat to examine the auditory function and the structure of the sensory epithelium. Rats received either HA or hydroxy-propyl-methyl-cellulose by trans-tympanic injection (middle ear cavity was completely filled up) and were compared to untreated, age- and weight-matched rats. In both treated groups ABR revealed transitory, mild conduction hearing loss, in particular for high frequencies, until day 7 postinjection. This loss recovered completely within the 15th day. Morphologically, no significant degenerative/necrotic lesions were observed in the organ of Corti, from both treated groups.

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“…The biodegradability of HA in the ME is well established. On average, the resorption period of exogenous 1.9% HA in the ME cavity of rats is 4 to 12 weeks,80–83 which is optimal in providing adequate time for healing and support prior to eliciting an inflammatory foreign body response. In contrast to Gelfoam, the elimination of HA is through the eustachian tube instead of reabsorption by the ME mucosa or the surrounding tissues 84, 85.…”

“…Transtympanic application (1.9% HA), implantation in the oval window niche (1% HA), and through the punctured round window membrane (1% HA) were all shown to be free of toxicity in the cochlea and vestibular system 80, 86, 88, 89. Although some conductive hearing loss, mainly low and middle frequencies (2–8 kHz), has been reported, it is only temporary and reversible 82, 83, 90. This possibly occurs due to osmotic changes exerted by HA in the inner ear,90–92 or mechanical damping caused by HA residues 80, 82.…”

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“…502 The hearing loss depends on the amount of gel injected in the middle ear (Feng et al, 2014). 503 However, the presence of chitosan (Saber et al, 2010), hyaluronic acid (Martini et al, 1992)or 504 poloxamer 407 hydrogels in the middle eardid not provoke any 505 histological damages to the round window and the cochlea indicating that those hydrogels 506 have no noxious effects by themselves. The hearing loss observed is thus conductive in 507 nature, i.e.…”

“…In most studies describedpreviously, perilymphatic drug levels are In most studies, a conductive transient hearing loss was observed when the middle ear 500 cavity was overfilled with gel. In all cases, the hearing function returned to normal within 7 501 to 10 days (Martini et al, 1992, Paulson et al, 2008. 502 The hearing loss depends on the amount of gel injected in the middle ear (Feng et al, 2014).…”

“…In addition, shear-thinning and self-healing hydrogels 455 such as hyaluronic acid are also interesting since their viscosity decreases under shear during 456 injection andis rapidly recovered after injection (El Kechai et al, 2015). (Martini et al, 1992). 469 …”