Systemic aminoglycosides are trafficked via endolymph into cochlear hair cells

Li, Hongzhe; Steyger, Peter S.

doi:10.1038/srep00159

“…Hair cells are readily damaged by aminoglycosides. Evidence suggests that aminoglycosides are preferentially transported into the inner ear extracellular fluid 32 and then enter hair cells through their mechanotransduction channels 33 . Although the intracellular site of action is not …”

Section: Otitis Mediamentioning

confidence: 99%

New treatment options for hearing loss

Müller

¹

,

Barr-Gillespie

²

2015

Nat Rev Drug Discov

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Hearing loss is the most common form of sensory impairment in humans and affects more than 40 million people in the United States alone. No drug-based therapy has been approved by the Food and Drug Administration, and treatment mostly relies on devices such as hearing aids and cochlear implants. Over recent years, more than 100 genetic loci have been linked to hearing loss and many of the affected genes have been identified. This understanding of the genetic pathways that regulate auditory function has revealed new targets for pharmacological treatment of the disease. Moreover, approaches that are based on stem cells and gene therapy, which may have the potential to restore or maintain auditory function, are beginning to emerge.

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“…However, these drugs have significant risks of nephrotoxicity and ototoxicity [21] . In the inner ear, systemic aminoglycosides cross the blood-labyrinth barrier (BLB) and can damage cochlear hair cells through several mechanisms such as apoptosis or release of reactive oxygen species (ROS), leading to permanent sensorineural hearing loss [22,23] . GM not only damages the vestibular hair cell but also otoconia [24,6] .…”

Section: Discussionmentioning

confidence: 99%

Protective Effect of Ginkgo Biloba Extract on Gentamicin-Induced Structural Changes of Calcite-Gelatin Composite

Jang

¹

,

Cho²,

Lee³

2016

Int Adv Otol

0

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OBJECTIVE:To evaluate the protective effect of Ginkgo biloba extract (GBE) on gentamicin (GM)-induced morphological damage of an artificial otoconia. MATERIALS and METHODS:An artificial otoconia powder was placed in a 12-well culture plate containing artificial endolymph. GM (500 μL; 40 mg/mL) was added to the first four wells. GM (500 μL; 40 mg/mL) with GBE (500 μL) was added to the next four wells. PBS (500 μL) was added to the remaining four wells as a control. The levels of nitric oxide (NO) synthesis were determined in the supernatants of each group. Alteration in surface morphology and calcium content were determined by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX), respectively. RESULTS:NO concentration increased in the GM-treated group compared with that in the control group. When the calcite-gelatin composite was treated with GBE, GM-stimulated NO production significantly decreased. The surface of the calcite-gelatin composite exposed to GM showed erosive fissures and had a honeycomb-like appearance. GBE showed a protective effect against dissolution. EDX showed that the calcium content of the GM-treated group significantly decreased. However, the GBE-treated group demonstrated an insignificant change in the calcium concentration compared with the control. CONCLUSION:From these results, we can conclude that GBE may have a protective effect against GM-induced NO production and superficial structural changes.

show abstract

“…However, these drugs have significant risks of nephrotoxicity and ototoxicity [21] . In the inner ear, systemic aminoglycosides cross the blood-labyrinth barrier (BLB) and can damage cochlear hair cells through several mechanisms such as apoptosis or release of reactive oxygen species (ROS), leading to permanent sensorineural hearing loss [22,23] . GM not only damages the vestibular hair cell but also otoconia [24,6] .…”

Section: Discussionmentioning

confidence: 99%

Untitled

2016

Int Adv Otol

0

View full text Add to dashboard Cite

OBJECTIVE:To evaluate the protective effect of Ginkgo biloba extract (GBE) on gentamicin (GM)-induced morphological damage of an artificial otoconia. MATERIALS and METHODS:An artificial otoconia powder was placed in a 12-well culture plate containing artificial endolymph. GM (500 μL; 40 mg/mL) was added to the first four wells. GM (500 μL; 40 mg/mL) with GBE (500 μL) was added to the next four wells. PBS (500 μL) was added to the remaining four wells as a control. The levels of nitric oxide (NO) synthesis were determined in the supernatants of each group. Alteration in surface morphology and calcium content were determined by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX), respectively. RESULTS:NO concentration increased in the GM-treated group compared with that in the control group. When the calcite-gelatin composite was treated with GBE, GM-stimulated NO production significantly decreased. The surface of the calcite-gelatin composite exposed to GM showed erosive fissures and had a honeycomb-like appearance. GBE showed a protective effect against dissolution. EDX showed that the calcium content of the GM-treated group significantly decreased. However, the GBE-treated group demonstrated an insignificant change in the calcium concentration compared with the control. CONCLUSION:From these results, we can conclude that GBE may have a protective effect against GM-induced NO production and superficial structural changes.

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Systemic aminoglycosides are trafficked via endolymph into cochlear hair cells

Cited by 84 publications

References 25 publications

New treatment options for hearing loss

New treatment options for hearing loss

Protective Effect of Ginkgo Biloba Extract on Gentamicin-Induced Structural Changes of Calcite-Gelatin Composite

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