Effect of intratympanic dexamethasone, memantine and piracetam on cellular apoptosis due to cisplatin ototoxicity

Abstract

Dexamethasone and memantine were found superior to piracetam in reducing apoptosis due to cisplatin ototoxicity. Further studies of this subject are needed, incorporating electron microscopy and auditory brainstem response testing.

Dexamethasone Protects Against Apoptotic Cell Death of Cisplatin-exposed Auditory Hair Cells In Vitro

“…In the guinea pig, DXM diffusion across the round window membrane results in a DXM concentration gradient in the perilymph of the scala tympani (13); the lowest DXM concentrations occur farthest from the round window membrane at the apical turn and the highest concentrations are present in the basal turn where cisplatin ototoxicity is most prominent. However, IT DXM has demonstrated variable effects against cisplatin induced hearing loss in vivo (5)(6)(7)(8)(9)(10)(11). One randomized clinical trial of 15 patients demonstrated that IT DXM can reduce hearing threshold shifts at 6000 Hz and lower OHC dysfunction as determined by the distortion product otoacoustic emissions (4000-8000 Hz); the results were significant despite a small sample size (12).…”

“…No significant protection of OHC viability of the basal turn was observed at a lower dose of DXM (i.e., 75 mg/mL) in explants exposed to 2, 5, and 10 mM of cisplatin in vitro. These findings suggest that the variability in IT DXM protection against cisplatin ototoxicity demonstrated in animal and human studies may be a result of insufficient levels of DXM accumulating in the perilymph fluid within the scala tympani of the inner ear (4)(5)(6)(7)(8)(9)(10)(11).…”

“…The degree of IT DXM protection varies between published in vivo and clinical studies of cisplatin-induced hearing loss and is thought to be the result of the intrinsic properties of DXM and various factors that prevent adequate delivery of DXM into the inner ear (i.e., dosage, duration, degree of passive diffusion of DXM across the round window membrane) (5)(6)(7)(8)(9)(10)(11)(12). However, the results of this in vitro study support the use of DXM as a treatment to reduce and/or prevent cisplatin ototoxicity and continued research in improving DXM delivery into the inner ear, as DXM protected against cisplatin induced OHC loss in a dose-dependent fashion with complete protection observed at higher doses of dexamethasone.…”

“…There are only a few published studies of small sample size that suggest DXM can abrogate hearing threshold shifts in high frequencies after cisplatin exposure in vivo, and there is only one human clinical trial published that demonstrates some protection with DXM (5)(6)(7)(8)(9)(10)(11)(12). The variability in the effects of IT DXM in cisplatin ototoxicity in rodents and humans may be related to how effective DXM can traverse the round window membrane and enter into the inner ear.…”

Does systemic steroid deficiency affect inner ear functions?

“…The effects of corticosteroids on the inner ear have been reported to increase anti-ROS enzyme activity in the cochlea, to decrease inflammatory molecule formation, and to reduce inner cell apoptosis induced by ototoxicity [1][2][3][4]. Steroids are used for treating various ear pathologies such as sudden sensorineural hearing loss, hearing loss due to noise exposure, Meniere's disease, salicylate and aminoglycoside ototoxicity [1,2,5].…”