Effect of intratympanic dexamethasone administration on cisplatin-induced ototoxicity in adult guinea pigs

Shafik, Amr G.; El-Kabarity, Rasha H.; Thabet, Mirahan T.; Bahaa, Nevine; Kalleny, Nagwa Kostandy

doi:10.1016/j.anl.2012.05.010

Cited by 28 publications

(34 citation statements)

References 42 publications

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“…Those receptors have been shown predominantly in the spiral ligament, and then organ of Corti and stria vascularis in the human inner ear [20] . Ion homeostasis, immune suppression, and free radical scavenging effects of those agents made them to be used to protect cochlea, particularly in ototoxic drug use and acoustic trauma [21] . The results of this study suggest that dexamathasone has a protective effect for gentamicin toxicity.…”

Section: Discussionmentioning

confidence: 99%

Selective Window Application of Gentamicin Dexamethasone in Meniere's Disease

Ardıç

Tümkaya²,

Aykal³

et al. 2017

Int Adv Otol

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OBJECTIVE:The purpose of the study is to prevent hearing loss when using intratympanic (IT) gentamicin for intractable Meniere's disease. MATERIALS and METHODS:It is a retrospective case review study. Twenty five patients who had definite Meniere's disease and had either selective window application or weekly IT gentamicin were included into the study. First group (selective) had dexamethasone on the round window and gentamicin on oval window during exploratory tympanotomy procedure. The second group had IT gentamicin at weekly intervals. The degree of caloric weakness (CW), average hearing level in low pitch (HLP) (250, 500, 1000, 2000 Hz) and high pitch (HHP) (4000, 6000, 8000 Hz) were compared before and after treatment. The need for further treatment was noted. RESULTS:In the first group, the average HLP was increased from 51.6±7dB to 52.2±5.6 dB. The average HHP was increased 41.96±20.2 dB to 47.2±18.3 dB after treatment. The CW changed from 37.6±23.9 % to 54.6±30.6 %. In the second group, the average HLP was increased from 56.3±10.5 dB to 61.65±18.3 dB. The average HHP was increased 59.05±17.4 dB to 69.4±21.98 dB after treatment. The CW changed from 45.8±22.3% to 71.53±29.63 %. Both methods had statisticaly significant increase in caloric weakness. But only IT gentamicin led a significant hearing loss in HHP. CONCLUSION:The use of dexamethasone and gentamycin via different windows in the middle ear is safe and effective method for Meniere's disease in the short term. Application of dexamethasone protects not only the hearing cells but vestibular cells also.

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Section: Discussionmentioning

confidence: 99%

Selective Window Application of Gentamicin Dexamethasone in Meniere's Disease

Ardıç

Tümkaya²,

Aykal³

et al. 2017

Int Adv Otol

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“…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.…”

mentioning

confidence: 99%

“…This would result in less damage at the base of the cochlea, which might be further protected by the intratympanic application of DEX. 15,16 …”

mentioning

confidence: 99%

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

Sun¹,

Wang²,

Zheng³

et al. 2015

IJN

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This study aimed to investigate the sustained drug release properties and hearing protection effect of polyethylene glycol-coated polylactic acid (PEG-PLA) stealth nanoparticles loaded with dexamethasone (DEX). DEX was fabricated into PEG-PLA nanoparticles using an emulsion and evaporation technique, as previously reported. The DEX-loaded PEG-PLA nanoparticles (DEX-NPs) had a hydrodynamic diameter of 130±4.78 nm, and a zeta potential of −26.13±3.28 mV. The in vitro release of DEX from DEX-NPs lasted 24 days in phosphate buffered saline (pH 7.4), 5 days in artificial perilymph (pH 7.4), and 1 day in rat plasma. Coumarin 6-labeled NPs placed onto the round window membrane (RWM) of guinea pigs penetrated RWM quickly and accumulated to the organs of Corti, stria vascularis, and spiral ganglion cells after 1 hour of administration. The DEX-NPs locally applied onto the RWM of guinea pigs by a single-dose administration continuously released DEX in 48 hours, which was significantly longer than the free DEX that was cleared out within 12 hours after administration at the same dose. Further functional studies showed that locally administrated single-dose DEX-NPs effectively preserved outer hair cells in guinea pigs after cisplatin insult and thus significantly attenuated hearing loss at 4 kHz and 8 kHz frequencies when compared to the control of free DEX formulation. Histological analyses indicated that the administration of DEX-NPs did not induce local inflammatory responses. Therefore, prolonged delivery of DEX by PEG-PLA nanoparticles through local RWM diffusion (administration) significantly protected the hair cells and auditory function in guinea pigs from cisplatin toxicity, as determined at both histological and functional levels, suggesting the potential therapeutic benefits in clinical applications.

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“…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).…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

mentioning

confidence: 99%