Recovery of Hearing in Cisplatin-Induced Ototoxicity in the Guinea Pig with Intratympanic Dexamethasone

Abstract

The purpose of this study was to investigate the effectiveness of intratympanic dexamethasone injection as a therapeutic agent against cisplatin-induced ototoxicity. Animals were randomly divided into three groups. Group one received intraperitoneal cisplatin alone, group two, received intratympanic dexamethasone after cisplatin ototoxicity had been demonstrated. Group three, which is control group, received intratympanic dexamethasone.Then we made three measurements. First we measured the baseline distortion product otoacustic emission (DPOAEs) of all the guine pigs. Second we injected cisplatin intraperitoneal group one and two the same day. Third we measured DPOAEs after 72 h of group one and two. Moreover DPOAEs were measured at the end of the first and second week only in group two. Cochleae were harvested and processed for electron microscopy after then. Values of The DPOAEs amplitudes and signal-to-noise ratio (SNR) at 1-6 kHz frequencies for group 1 after the injections significantly decreased over those before injections (P \ 0.05). In group 3, there were no significant differences in DPOAE amplitude and SNR values When they are compare before and after their intratympanic dexamethasone injections (P [ 0.05). In group 2, the DPOAEs measurements were close to significance at the end of the second week (P = 0.056). Intratympanic dexamethasone injection did not cause any ototoxic effect. Although intratympanic dexamethasone did not reach the statistically significant results, the measurements were close to significance. Intratympanic dexamethasone might have a significant therapeutic effect after cisplatin ototoxicity with different dose and application regimens.

A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration

“…12 Recently, several studies have demonstrated that the intratympanic delivery of DEX minimized cisplatin-induced hearing in a frequency-related manner. [14][15][16][17] The efficiency of this strategy in treating cisplatin-induced ototoxicity was further confirmed clinically. 7 To date, the results obtained for the intratympanic delivery of glucocorticoids varied, highly depending on the dose, frequency, intensity of the cisplatin injection, and the animal models used in the experiments.…”

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.…”