Aspirin attenuates gentamicin ototoxicity: From the laboratory to the clinic

Yang, Chen; Huang, Wei; Zha, Dingjun; Qiu, Jianyin; Wang, Jin Ling; Sha, Su Hua; Schacht, Jochen

doi:10.1016/j.heares.2006.05.008

Cited by 120 publications

(96 citation statements)

References 34 publications

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“…Cochlear implant users vary widely in their ability to perceive speech (Firszt et al 2004;Zeng 2004;Wilson and Dorman 2008). Much of that variability is apparently due to differences in the survival and plasticity of neural substrates available to electrodes (e.g., cochlear nerve axons, the cochlear nucleus neurons upon which they synapse, and other brainstem and midbrain nuceli en route to auditory cortex), prompting efforts to preserve those substrates through anticipatory pharmacologic protection from ototoxic agents (Chen et al 2007); intralabyrinthine delivery of growth factors, stem cells, and gene therapy (Hendricks et al 2008); and, when no better alternative exists, prompt implantation and delivery of neuroprotective prosthetic input (Ryugo et al 2005;Stakhovskaya et al 2008).…”

Section: Key Differences Between Natural and Prosthetic Ampullary Nermentioning

confidence: 99%

Vestibulo-Ocular Reflex Responses to a Multichannel Vestibular Prosthesis Incorporating a 3D Coordinate Transformation for Correction of Misalignment

Fridman

Davidovics

Dai

et al. 2010

JARO

128

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There is no effective treatment available for individuals unable to compensate for bilateral profound loss of vestibular sensation, which causes chronic disequilibrium and blurs vision by disrupting vestibulo-ocular reflexes that normally stabilize the eyes during head movement. Previous work suggests that a multichannel vestibular prosthesis can emulate normal semicircular canals by electrically stimulating vestibular nerve branches to encode head movements detected by mutually orthogonal gyroscopes affixed to the skull. Until now, that approach has been limited by current spread resulting in distortion of the vestibular nerve activation pattern and consequent inability to accurately encode head movements throughout the full 3-dimensional (3D) range normally transduced by the labyrinths. We report that the electrically evoked 3D angular vestibulo-ocular reflex exhibits vector superposition and linearity to a sufficient degree that a multichannel vestibular prosthesis incorporating a precompensatory 3D coordinate transformation to correct misalignment can accurately emulate semicircular canals for head rotations throughout the range of 3D axes normally transduced by a healthy labyrinth.

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Section: Key Differences Between Natural and Prosthetic Ampullary Nermentioning

confidence: 99%

Vestibulo-Ocular Reflex Responses to a Multichannel Vestibular Prosthesis Incorporating a 3D Coordinate Transformation for Correction of Misalignment

Fridman

Davidovics

Dai

et al. 2010

JARO

128

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“…In addition, it has been hypothesized that aminoglycosides may form cochleotoxic metabolites. Antioxidants apparently attenuate aminoglycosideinduced hearing loss, pointing to a role of the mitochondrion, an organelle involved in oxidation, as a target of ototoxic drugs (7,8). Genetic analyses of individuals hypersensitive to aminoglycosides have identified mutations in mitochondrial rRNA.…”

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confidence: 99%

Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome as target in aminoglycoside ototoxicity

Hobbie

Subramanian

Kalapala

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

164

180

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Aminoglycoside ototoxicity has been related to a surprisingly large number of cellular structures and metabolic pathways. The finding that patients with mutations in mitochondrial rRNA are hypersusceptible to aminoglycoside-induced hearing loss has indicated a possible role for mitochondrial protein synthesis. To study the molecular interaction of aminoglycosides with eukaryotic ribosomes, we made use of the observation that the drug binding site is a distinct domain defined by the small subunit rRNA, and investigated drug susceptibility of bacterial hybrid ribosomes carrying various alleles of the eukaryotic decoding site. Compared to hybrid ribosomes with the A site of human cytosolic ribosomes, susceptibility of mitochondrial hybrid ribosomes to various aminoglycosides correlated with the relative cochleotoxicity of these drugs. Sequence alterations that correspond to the mitochondrial deafness mutations A1555G and C1494T increased drug-binding and rendered the ribosomal decoding site hypersusceptible to aminoglycoside-induced mistranslation and inhibition of protein synthesis. Our results provide experimental support for aminoglycoside-induced dysfunction of the mitochondrial ribosome. We propose a pathogenic mechanism in which interference of aminoglycosides with mitochondrial protein synthesis exacerbates the drugs' cochlear toxicity, playing a key role in sporadic dosedependent and genetically inherited, aminoglycoside-induced deafness.decoding ͉ mitochondria ͉ ribosomes ͉ toxicity ͉ translation

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“…Damage to hair cells exposed to aminoglycosides appears to be caused by a release of large quantities of reactive oxygen species, or free radicals, into the hair cell cytoplasm (Chen et al, 2007;Schacht, 2007). Most cells release small quantities of free radicals as a byproduct of their normal metabolic processes and they have specific buffers that bind up these free radicals to keep them from damaging the cell.…”

Section: Therapeutic Intervention In Hair Cell Apoptosismentioning

confidence: 99%

“…It has been proposed that if we could supply the cochlea with additional free radical buffers during the drug exposure this abundance of buffers may be able to bind up all the excess free radicals and avert the initiation of apoptosis in the hair cells. Animal studies and pre-clinical trials in humans show support for this hypothesis by demonstrating a reduction in hair cell loss and functional impairment when subjects were treated systemically or directly into the middle ear with free radical scavengers (Campbell & Rybak, 2007;Chen et al, 2007;Rybak, Whitworth, Mukherjea, & Ramkumar, 2007). Thus, future therapies for preventing hearing loss may include systemic or localized application of free radical scavengers to prevent the buildup of reactive oxygen species during or shortly after a traumatic event.…”

Section: Therapeutic Intervention In Hair Cell Apoptosismentioning

confidence: 99%

Genetic and pharmacological intervention for treatment/prevention of hearing loss

Cotanche

2008

Journal of Communication Disorders

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Twenty years ago it was first demonstrated that birds could regenerate their cochlear hair cells following noise damage or aminoglycoside treatment. An understanding of how this structural and functional regeneration occurred might lead to the development of therapies for treatment of sensorineural hearing loss in humans. Recent experiments have demonstrated that noise exposure and aminoglycoside treatment lead to apoptosis of the hair cells. In birds, this programmed cell death induces the adjacent supporting cells to undergo regeneration to replace the lost hair cells. Although hair cells in the mammalian cochlea undergo apoptosis in response to noise damage and ototoxic drug treatment, the supporting cells do not possess the ability to undergo regeneration. However, current experiments on genetic manipulation, gene therapy, and stem cell transplantation suggest that regeneration in the mammalian cochlea may eventually be possible and may 1 day provide a therapeutic tool for hearing loss in humans.Learning outcomes-The reader should be able to: (1) Describe the anatomy of the avian and mammalian cochlea, identify the individual cell types in the organ of Corti, and distinguish major features that participate in hearing function, (2) Demonstrate a knowledge of how sound damage and aminoglycoside poisoning induce apoptosis of hair cells in the cochlea, (3) Define how hair cell loss in the avian cochlea leads to regeneration of new hair cells and distinguish this from the mammalian cochlea where there is no regeneration following damage, and (4) Interpret the potential for new approaches, such as genetic manipulation, gene therapy and stem cell transplantation, could provide a therapeutic approach to hair cell loss in the mammalian cochlea.

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Aspirin attenuates gentamicin ototoxicity: From the laboratory to the clinic

Cited by 120 publications

References 34 publications

Vestibulo-Ocular Reflex Responses to a Multichannel Vestibular Prosthesis Incorporating a 3D Coordinate Transformation for Correction of Misalignment

Vestibulo-Ocular Reflex Responses to a Multichannel Vestibular Prosthesis Incorporating a 3D Coordinate Transformation for Correction of Misalignment

Genetic analysis of interactions with eukaryotic rRNA identify the mitoribosome as target in aminoglycoside ototoxicity

Genetic and pharmacological intervention for treatment/prevention of hearing loss

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