Comparison of the protective effects of intratympanic dexamethasone and methylprednisolone against cisplatin-induced ototoxicity

Özel, Halil Erdem; Özdoğan, Fatih; Gürgen, Seren Gülşen; Esen, Erkan; Genç, Selahattin; Selçuk, Adın

doi:10.1017/s0022215115003473

Cited by 26 publications

(22 citation statements)

References 21 publications

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“…15,16 However, systemic administration of DEX led to antitumor interference with CDDP due to the downregulation of apoptosis gene. 17 Moreover, intratympanic administration of DEX has yielded conflicting results, owing to the elimination of the drug through the eustachian tube, rapid clearance of drugs, and nonspecific distribution in the inner ear. Nanotechnologies have advantages such as sustained release and specific targeting, which have attracted great attention in the past decades for delivering agents to the inner ear.…”

Section: Introductionmentioning

confidence: 99%

A666-conjugated nanoparticles target prestin of outer hair cells preventing cisplatin-induced hearing loss

Wang¹,

Chen²,

Tao³

et al. 2018

IJN

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BackgroundThe delivery of treatment agents to inner ear with drug delivery system (DDS) has been under investigation to overcome the limitations of the conventional therapeutic agents in curing or alleviating the cisplatin ototoxicity.MethodsIn the present study, a novel targeted dexamethasone (DEX)-loaded DDS, A666-DEX-NP, was constructed for prevention from cisplatin-induced hearing loss. A666-(CLEPRWGFGWWLH) peptides specifically bind to prestin, which is limited to the outer hair cells (OHCs). HEI-OC1 and cisplatin-treated guinea pigs (12 mg/kg, intraperitoneal) were used as in vitro and in vivo models for investigating the targeting and protective efficiency against cisplatin.ResultsAs expected, compared to A666-unconjugated nanoparticles (NP), A666-conjugated coumarin 6-labeled NP showed active targeting to OHCs. Furthermore, A666-coumarin 6-labeled NP could be significantly internalized by HEI-OC1 cells via the A666–prestin interaction. This facilitated the uptake of cells pretreated with A666-DEX-NP, followed by the cisplatin-treated group, which led to enhanced cell viability, reduced apoptotic properties, and decreased reactive oxygen species levels as compared to cells pretreated with DEX or DEX-NP, 4 hours in advance of cisplatin treatment. In cisplatin-treated guinea pigs, pretreatment with A666-DEX-NP effectively preserved OHCs and showed significant hearing protection at 4, 8, and 16 kHz as compared to pretreatment with saline, DEX, or DEX-NP formulation.ConclusionThis OHC-targeting DDS provides a novel strategy for DEX application that can be potentially used to combat cisplatin ototoxicity.

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Section: Introductionmentioning

confidence: 99%

A666-conjugated nanoparticles target prestin of outer hair cells preventing cisplatin-induced hearing loss

Wang¹,

Chen²,

Tao³

et al. 2018

IJN

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“…26 This loss typically starts at the first row of OHCs in the basal turn of cochlea, followed by the other OHC rows. 21,26,27 With increasing doses or prolonged administration, it progresses towards more apically located cochlear turns and, eventually, to the single row of inner hair cells. 26 Studies have shown that cisplatin causes an increase in auditory threshold due to the blockade of ion transduction International Journal of Hematology and Oncology channels and degeneration of sensory cells.…”

Section: Discussionmentioning

confidence: 99%

“…In experimental studies 19,21,23 , it was observed that the area damaged in cochlea after cisplatin administration was the organ of Corti accompanied by OHC loss, and even though this damage was more severe in the basal turn, it was observed in all turns of cochlea. Our SEM findings in the cisplatin group showed severe damage in the OHCs at the basal and middle turn of cochlea compared to the control group and the cisplatin/steroid group.…”

Section: Discussionmentioning

confidence: 99%

“…Our SEM findings in the cisplatin group showed severe damage in the OHCs at the basal and middle turn of cochlea compared to the control group and the cisplatin/steroid group. In several experimental studies, protective agents against cisplatin ototoxicity have been used through systemic 19 or intratympanic 21 routes. With the intratympanic method, the protective agent reaches inner ear directly and with a high concentration without affecting other organs, and systemic side effects are quite fewer.…”

Section: Discussionmentioning

confidence: 99%

“…32 The use of intratympanic protective agents to prevent cisplatin-induced ototoxicity has been investigated in animal models, but most studies have focused on intratympanic glucocorticoids. [11][12][13]15,21,27 The underlying reason of using corticosteroids may be the reduced inflammation by autoimmune dysfunction through the immune effects, or the direct effects on the inner ear neuroepithelium. 11 Proposed mechanisms of action include the notion that steroids move through the round window, improve cellular oedema and metabolic disorders of the inner ear, provide membrane stabilisation and suppress irritative or hypersensitive conditions in sensory cells of the inner ear through sedative effects.…”

Section: Discussionmentioning

confidence: 99%

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Effects of Intratympanic Steroid on Cisplatin Ototoxicity: An Electrophysiological and Ultrastructural Study

Taş¹

2018

UHOD

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Ototoxicity refers to the inner ear dysfunction caused by a drug or a chemical agent which manifests as hearing loss or balance impairment, or both. Currently, antibiotics, diuretics, anti-inflammatory drugs, antineoplastic agents, antimalarial drugs and some other agents are known to cause ototoxicity. Cisplatin is an antineoplastic agent for which the ototoxicity incidence may vary based on the treatment protocol. In the present study, we aimed to perform an electrophysiological and ultrastructural evaluation regarding the protective effectiveness of intratympanic steroids on cisplatin ototoxicity. Electrophysiological assessment included tympanometry and auditory brainstem response (ABR), and 16 guinea pigs (32 ears) with normal hearing were randomly assigned to 4 groups as follows: control, cisplatin, cisplatin/steroid and cisplatin/physiological saline. Following the electrophysiological measurements, temporal bones were dissected for ultrastructural examinations. In the cisplatin group, a statistically significant (p< 0.05) threshold difference was noted for the ABR test versus the other groups while this threshold difference was lower in the cisplatin/steroid group compared to the other groups. Ultrastructural evaluations revealed abnormal outer hair cell stereocilia morphology and severe degenerative changes in the cisplatin and cisplatin/physiological saline groups. Mild degenerative alterations were seen in the outer hair cell stereocilia morphology in the guinea pig cochlea administered with intratympanic steroid. We believe intratympanic steroid administration showed protective effectiveness on the cisplatin-induced ototoxic damage in our study.

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Clinical trials evaluating transtympanic otoprotectants for cisplatin-induced ototoxicity: what do we know so far?

Waissbluth

2020

Eur Arch Otorhinolaryngol

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Comparison of the protective effects of intratympanic dexamethasone and methylprednisolone against cisplatin-induced ototoxicity

Abstract: Dexamethasone (and possibly methylprednisolone) may be clinically useful as an intratympanic chemopreventive agent to treat cisplatin ototoxicity. Future clinical studies should investigate the use of dexamethasone for this purpose in adult patients.

Cited by 26 publications

References 21 publications

A666-conjugated nanoparticles target prestin of outer hair cells preventing cisplatin-induced hearing loss

A666-conjugated nanoparticles target prestin of outer hair cells preventing cisplatin-induced hearing loss

Effects of Intratympanic Steroid on Cisplatin Ototoxicity: An Electrophysiological and Ultrastructural Study

Clinical trials evaluating transtympanic otoprotectants for cisplatin-induced ototoxicity: what do we know so far?

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