Objective Method for Differentiating Between Drug-Induced Vestibulotoxicity and Cochleotoxicity

Freeman, Sharon; Priner, Ronit; Elidan, Josef; Sohmer, Haim

doi:10.1097/00129492-200101000-00014

Cited by 8 publications

(12 citation statements)

References 35 publications

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“…Similar findings for vestibular function have been described before [Freeman et al, , 2001Plotnik et al, 1999;Jones et al, 2001]. Gentamicin treatment had more effect on VsEP outcomes when stimulated in the 2 horizontal planes than in the vertical plane ( fig.…”

Section: Effects Of Gentamicin Treatmentsupporting

confidence: 86%

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Combined Administration of Kanamycin and Furosemide Does Not Result in Loss of Vestibular Function in Guinea Pigs

Bremer

Groot²,

Versnel³

et al. 2011

Audiol Neurotol

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Aminoglycoside antibiotics are known to damage the vestibular and auditory sensory epithelia. Although loop diuretics enhance the cochleotoxic effect of aminoglycosides, it is not known whether concomitant administration of an aminoglycoside and a loop diuretic affects the vestibular system. The aim of our study was to investigate the effect of co-administration of kanamycin and furosemide upon the otolith organs and to compare it to the known vestibulotoxic effect of gentamicin. Five guinea pigs were injected with a single dose of both kanamycin (400 mg/kg, s.c.) and furosemide (100 mg/kg, i.v.), 5 animals received gentamicin (100 mg/kg, i.p.) for 10 days, and 5 untreated animals served as controls. After 7 days, vestibular function was assessed by measuring vestibular short-latency evoked potentials (VsEPs) to linear acceleration stimuli and cochlear function by auditory brainstem responses (ABRs) to clicks. Hair cell densities were determined in phalloidin-stained whole mounts of the utricles and saccules, and in midmodiolar sections of resin-embedded cochleae. Co-administration of kanamycin and furosemide had no significant effect on VsEPs and hair cell densities in the utricles and saccules were not reduced. ABR thresholds were increased to a great extent (by ∼60 dB), and histologically a severe loss of cochlear hair cells was observed. The effect of gentamicin, both on vestibular and cochlear function, was just the opposite. VsEP thresholds to horizontal stimulation were elevated and suprathreshold amplitudes showed a decrease, whereas cochlear function was not reduced. With this protocol, we have a tool to selectively induce cochlear or vestibular damage, which may be of interest to researchers and clinicians alike.

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Section: Effects Of Gentamicin Treatmentsupporting

confidence: 86%

“…As furosemide temporarily decreases the endolymphatic potential [Sewell, 1984], it may thus affect cochlear function. However, furosemide alone does not affect vestibular function [Freeman et al, , 2001, suggesting that the observed limited effect on the utricle may be due to kanamycin itself.…”

Section: Effects Of Combined Kanamycin and Furosemide Treatmentmentioning

confidence: 89%

Combined Administration of Kanamycin and Furosemide Does Not Result in Loss of Vestibular Function in Guinea Pigs

Bremer

Groot²,

Versnel³

et al. 2011

Audiol Neurotol

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“…Freeman et al [22] evaluated amikacin induced cochleotoxicity and vestibulotoxicity by measuring auditory brainstem responses (ABR) and vestibular evoked potentials. They found that cochleotoxic and vestibulotoxic effects emerged on days 7 and 17, respectively.…”

Section: Discussionmentioning

confidence: 99%

A Prospective Experimental Study on the Protective Effect of Resveratrol against Amikacin-Induced Ototoxicity in Rats

Avcı¹,

Erkan²,

Sönmez³

et al. 2016

Int Adv Otol

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OBJECTIVE:The purpose of this study was to evaluate the protective effect of resveratrol against amikacin-induced ototoxicity in rats by otoacoustic emission and histopathology of the cochlea. MATERIALS and METHODS:This study was conducted with 31 Sprague Dawley adult female rats that were 20-21 weeks old and 190-245 g in weight. Before the drug administration, distortion product otoacoustic emission (DPOAE) tests were performed in both ears of each rat. The rats were divided into four groups. Group 1 (n=7) received ethanol 1cc 4%, Group 2 (n=8) received 600 mg/kg amikacin, Group 3 (n=8) received 10 mg/kg resveratrol and 600 mg/kg amikacin, and Group 4 (n=8) received 1cc resveratrol at 10 mg/kg. The drugs were administered once a day for 21 consecutive days. Control DPOAE tests were performed at the 7 th , 14 th , and 21 st days after the administration of drugs. At the end of the study, the rats were sacrificed and their cochleae were dissected. The cochleae were evaluated for histopathologic changes. RESULTS:There was no statistically significant difference in the DPOAE measurements before the procedure between groups. The DPOAE measurements significantly decreased after the procedure in the amikacin group. There was no statistically significant difference in DPOAE measurements after the procedure in the amikacin + resveratrol, resveratrol, and ethanol groups. The histopathologic findings supported these results. CONCLUSION:We found that if resveratrol is administered with amikacin, the severity of amikacin-induced hearing loss is decreased. These findings suggest that resveratrol, a strong antioxidant, has a protective effect in amikacin ototoxicity.

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“…Similarly, studies of the ototoxicity of aminoglycosides, which are hydrophilic compounds, also noted discrepancies between vestibulotoxicity and cochleotoxicity (Freeman et al, 2001;Kitasato et al, 1990;Nakashima et al, 2000). Thus, susceptibility would rather depend on the selective sensitivity of cochlear and vestibular cells, than on the route of intoxication within the inner ear.…”

Section: Discussionmentioning

confidence: 99%

An in vitro model to assess the peripheral vestibulotoxicity of aromatic solvents

et al. 2021

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés. Copyright An in vitro model to assess the peripheral vestibulotoxicity of aromatic solvents Running title: In vitro screening of aromatic solvent vestibulotoxicity

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Objective Method for Differentiating Between Drug-Induced Vestibulotoxicity and Cochleotoxicity

Abstract: This study demonstrates the feasibility in general of using short-latency evoked potentials to evaluate functional cochleotoxicity and vestibulotoxicity of ototoxic drugs and to differentiate between them.

Cited by 8 publications

References 35 publications

Combined Administration of Kanamycin and Furosemide Does Not Result in Loss of Vestibular Function in Guinea Pigs

Combined Administration of Kanamycin and Furosemide Does Not Result in Loss of Vestibular Function in Guinea Pigs

A Prospective Experimental Study on the Protective Effect of Resveratrol against Amikacin-Induced Ototoxicity in Rats

An in vitro model to assess the peripheral vestibulotoxicity of aromatic solvents

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