Mechanisms of cisplatin ototoxicity: theoretical review

Gonçalves, Maiara Santos; Silveira, Aron Ferreira da; Teixeira, Adriane Ribeiro; Hyppolito, Miguel Ângelo

doi:10.1017/s0022215113000947

Cited by 70 publications

(65 citation statements)

References 60 publications

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“…1 The major dose-related adverse side effect of cisplatin treatment is irreversible sensorineural hearing loss. The reported rate of cisplatin-induced hearing loss ranges between 11% and 97%, with an average incidence of 62%.…”

Section: Introductionmentioning

confidence: 99%

“…An increase of malondialdehyde levels subsequently promotes the influx of calcium into the cochlear cells and triggers apoptosis. 1 Various researchers have attempted to develop effective otoprotective methods via the administration of antioxidants against ROS at an early stage in the ototoxic pathway. Unfortunately, many of the otoprotective agents inhibit the tumoricidal effects of cisplatin and/or have toxicities or unknown effects.…”

mentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

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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“…One of the dose-limiting side effects of cisplatin is ototoxicity, which manifests as tinnitus and/or bilateral sensorineural hearing loss in the clinical setting. [1][2][3][4] Ototoxicity caused by cisplatin has effects on a number of inner ear structures, including the stria vascularis, supporting cells, spiral ganglion cells, and outer hair cells (OHCs). 2,5,6 However, the OHCs appear to be the most susceptible to damage.…”

mentioning

confidence: 99%

“…[1][2][3][4] Ototoxicity caused by cisplatin has effects on a number of inner ear structures, including the stria vascularis, supporting cells, spiral ganglion cells, and outer hair cells (OHCs). 2,5,6 However, the OHCs appear to be the most susceptible to damage. There is evidence that the mechanism of ototoxicity is related to formation of reactive oxygen species that damage OHCs of the cochlea and trigger apoptosis.…”

mentioning

confidence: 99%

Cisplatin‐Induced Ototoxicity and the Effects of Intratympanic Diltiazem in a Mouse Model

Naples

Parham

2015

Otolaryngol.--head neck surg.

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Objective. To evaluate whether the calcium-channel blocker diltiazem has protective effects against cisplatin-induced ototoxicity in a mouse model. Study Design. Original basic science in vivo investigation.Setting. Academic setting: Otolaryngology-Head and Neck Surgery laboratory at University of Connecticut Health Center.Subjects. Thirty-nine female CBA/J mice.Methods. Pure tone-or click-evoked auditory brainstem responses (ABRs) were recorded in CBA/J mice to determine auditory thresholds. All mice had baseline ABRs recorded. They were then given a single cisplatin bolus (14 mg/kg), followed by 5 consecutive days of intratympanic diltiazem or saline control. Follow-up thresholds were recorded on days 7, 14, and 21 postcisplatin. Tone-evoked ABRs evaluated the otoprotective effect of 2-mg/kg diltiazem in 9 mice, and dose effect was examined in response to click-evoked ABR with 2-or 4-mg/kg diltiazem in 2 groups of 15 mice.Results. Saline-treated ears had significantly elevated toneevoked auditory thresholds when compared with diltiazemtreated ears (P = .038) on day 7 postcisplatin only. Clickevoked ABR thresholds were significantly elevated in salinetreated ears versus diltiazem-treated ears for the 2-mg/kg group (P = .001) and 4-mg/kg group (P = .011) on days 7, 14, and 21 postcisplatin. Conclusion.Intratympanic diltiazem has significant protective effects against cisplatin ototoxicity at 2 and 4 mg/kg. This is the first in vivo study to demonstrate that diltiazem offers a potentially novel therapy for cisplatininduced ototoxicity.

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“…This led to the accidental identification of cisdichloro-diammine-platinum (cisplatin; CDDP) as the agent responsible for this activity. Since then it opened a new era for the use of platinum compounds in the treatment of various solid malignant tumours, especially squamous cell cancers of the head and neck region, in both pediatric and adult age groups (Goncalves et al, 2013) also including testicular, ovarian, bladder, esophageal, small and non-small cell lung, breast, cervical, stomach and prostate cancers, as well as Hodgkin's and non-Hodgkin's lymphomas, neuroblastoma, sarcomas, multiple myeloma, melanoma, and mesothelioma (Florea et al, 2011).…”

Section: Historical Backgroundmentioning

confidence: 99%

Three Weekly Versus Weekly Cisplatin as Radiosensitizer in Head and Neck Cancer: a Decision Dilemma

Negi¹,

Kingsley²,

Srivastava³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Cisplatin-based concurrent chemoradiation plays an undisputed key role as definitive treatment in unresectable patients with locally advanced squamous cell carcinoma head and neck or as an organ preservation strategy. Treatment with 100 mg/m2 3-weekly cisplatin is considered the standard of care but is often associated with several adverse events. The optimum drug schedule of administration remains to be defined and presently, there is insufficient data limiting conclusions about the relative tolerability of one regimen over the other. This review addresses regarding the optimal dose schedule of cisplatin focusing mainly on three-weekly and weekly dose of cisplatin based concurrent chemoradiotherapy in locally advanced head and neck cancer with an emphasis on mucositis, dermatitis, systemic toxicity, compliance, and treatment interruptions. To derive a definitive conclusion, large prospective randomized trials are needed directly comparing standard 3-weekly cisplatin (100 mg/m 2 ) with weekly schedule (30 -40 mg/m 2 ) of concurrent cisplatin based chemoradiotherapy in locally advanced squamous cell carcinoma head and neck.

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Mechanisms of cisplatin ototoxicity: theoretical review

Abstract: Cisplatin ototoxicity proceeds via the formation of reactive oxygen species in cochlear tissue, with apoptotic cell death as a consequence.

Cited by 70 publications

References 60 publications

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

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

Cisplatin‐Induced Ototoxicity and the Effects of Intratympanic Diltiazem in a Mouse Model

Three Weekly Versus Weekly Cisplatin as Radiosensitizer in Head and Neck Cancer: a Decision Dilemma

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