Journal article
Natural Bizbenzoquinoline Derivatives Protect Zebrafish Lateral Line Sensory Hair Cells from Aminoglycoside Toxicity
Frontiers in cellular neuroscience, Vol.10(2016), pp.83-83
03/30/2016
Handle:
https://hdl.handle.net/2376/117754
PMCID: PMC4811916
PMID: 27065807
Abstract
Moderate to severe hearing loss affects 360 million people worldwide and most often results from damage to sensory hair cells. Hair cell damage can result from aging, genetic mutations, excess noise exposure, and certain medications including aminoglycoside antibiotics. Aminoglycosides are effective at treating infections associated with cystic fibrosis and other life-threatening conditions such as sepsis, but cause hearing loss in 20–30% of patients. It is therefore imperative to develop new therapies to combat hearing loss and allow safe use of these potent antibiotics. We approach this drug discovery question using the larval zebrafish lateral line because zebrafish hair cells are structurally and functionally similar to mammalian inner ear hair cells and respond similarly to toxins. We screened a library of 502 natural compounds in order to identify novel hair cell protectants. Our screen identified four bisbenzylisoquinoline derivatives: berbamine, E6 berbamine, hernandezine, and isotetrandrine, each of which robustly protected hair cells from aminoglycoside-induced damage. Using fluorescence microscopy and electrophysiology, we demonstrated that the natural compounds confer protection by reducing antibiotic uptake into hair cells and showed that hair cells remain functional during and after incubation in E6 berbamine. We also determined that these natural compounds do not reduce antibiotic efficacy. Together, these natural compounds represent a novel source of possible otoprotective drugs that may offer therapeutic options for patients receiving aminoglycoside treatment.
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Details
- Title
- Natural Bizbenzoquinoline Derivatives Protect Zebrafish Lateral Line Sensory Hair Cells from Aminoglycoside Toxicity
- Creators
- Matthew Kruger - School of Biological Sciences, Washington State UniversityRobert Boney - College of Arts and Sciences, Washington State UniversityAlexander J Ordoobadi - Department of Biology and Neuroscience Program, Amherst CollegeThomas F Sommers - Department of Biology and Neuroscience Program, Amherst CollegeJosef G Trapani - Department of Biology and Neuroscience Program, Amherst CollegeAllison B Coffin - School of Biological Sciences, Washington State University
- Publication Details
- Frontiers in cellular neuroscience, Vol.10(2016), pp.83-83
- Academic Unit
- Integrative Physiology and Neuroscience, Department of
- Publisher
- Frontiers Media S.A
- Grant note
- R15DC013900 / National Institute on Deafness and Other Communication Disorders
- Identifiers
- 99900548222201842
- Language
- English
- Resource Type
- Journal article