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Title: Fluvastatin protects cochleae from damage by high-level noise

Abstract

Exposure to noise and ototoxic drugs are responsible for much of the debilitating hearing loss experienced by about 350 million people worldwide. Beyond hearing aids and cochlear implants, there have been no other FDA approved drug interventions established in the clinic that would either protect or reverse the effects of hearing loss. Using Auditory Brainstem Responses (ABR) in a guinea pig model, we demonstrate that fluvastatin, an inhibitor of HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, protects against loss of cochlear function initiated by high intensity noise. A novel synchrotron radiation based X-ray tomographic method that imaged soft tissues at micrometer resolution in unsectioned cochleae, allowed an efficient, qualitative evaluation of the three-dimensional internal structure of the intact organ. For quantitative measures, plastic embedded cochleae were sectioned followed by hair cell counting. Protection in noise-exposed cochleae is associated with retention of inner and outer hair cells. This study demonstrates the potential of HMG-CoA reductase inhibitors, already vetted in human medicine for other purposes, to protect against noise induced hearing loss.

Authors:
ORCiD logo [1];  [2];  [2];  [2];  [3];  [4];  [4];  [5]
  1. Northwestern University Feinberg School of Medicine, Chicago, IL (United States). Department of Otolaryngology; Northwestern Univ., Evanston, IL (United States). Department of Biomedical Engineering and The Hugh Knowles Center, Department of Communication Sciences and Disorders
  2. Northwestern University Feinberg School of Medicine, Chicago, IL (United States). Department of Otolaryngology
  3. Northwestern University Feinberg School of Medicine, Chicago, IL (United States). Department of Cell and Molecular Biology
  4. Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
  5. Northwestern University Feinberg School of Medicine, Chicago, IL (United States). Department of Otolaryngology; Northwestern Univ., Evanston, IL (United States). The Hugh Knowles Center, Department of Communication Sciences and Disorders and Interdepartmental Neurosciences Program
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22); US Department of the Navy, Office of Naval Research (ONR)
OSTI Identifier:
1481415
Grant/Contract Number:  
AC02-06CH11357
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 8; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES

Citation Formats

Richter, Claus-Peter, Young, Hunter, Richter, Sonja V., Smith-Bronstein, Virginia, Stock, Stuart R., Xiao, Xianghui, Soriano, Carmen, and Whitlon, Donna S. Fluvastatin protects cochleae from damage by high-level noise. United States: N. p., 2018. Web. doi:10.1038/s41598-018-21336-7.
Richter, Claus-Peter, Young, Hunter, Richter, Sonja V., Smith-Bronstein, Virginia, Stock, Stuart R., Xiao, Xianghui, Soriano, Carmen, & Whitlon, Donna S. Fluvastatin protects cochleae from damage by high-level noise. United States. doi:10.1038/s41598-018-21336-7.
Richter, Claus-Peter, Young, Hunter, Richter, Sonja V., Smith-Bronstein, Virginia, Stock, Stuart R., Xiao, Xianghui, Soriano, Carmen, and Whitlon, Donna S. Wed . "Fluvastatin protects cochleae from damage by high-level noise". United States. doi:10.1038/s41598-018-21336-7. https://www.osti.gov/servlets/purl/1481415.
@article{osti_1481415,
title = {Fluvastatin protects cochleae from damage by high-level noise},
author = {Richter, Claus-Peter and Young, Hunter and Richter, Sonja V. and Smith-Bronstein, Virginia and Stock, Stuart R. and Xiao, Xianghui and Soriano, Carmen and Whitlon, Donna S.},
abstractNote = {Exposure to noise and ototoxic drugs are responsible for much of the debilitating hearing loss experienced by about 350 million people worldwide. Beyond hearing aids and cochlear implants, there have been no other FDA approved drug interventions established in the clinic that would either protect or reverse the effects of hearing loss. Using Auditory Brainstem Responses (ABR) in a guinea pig model, we demonstrate that fluvastatin, an inhibitor of HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway, protects against loss of cochlear function initiated by high intensity noise. A novel synchrotron radiation based X-ray tomographic method that imaged soft tissues at micrometer resolution in unsectioned cochleae, allowed an efficient, qualitative evaluation of the three-dimensional internal structure of the intact organ. For quantitative measures, plastic embedded cochleae were sectioned followed by hair cell counting. Protection in noise-exposed cochleae is associated with retention of inner and outer hair cells. This study demonstrates the potential of HMG-CoA reductase inhibitors, already vetted in human medicine for other purposes, to protect against noise induced hearing loss.},
doi = {10.1038/s41598-018-21336-7},
journal = {Scientific Reports},
number = 1,
volume = 8,
place = {United States},
year = {2018},
month = {2}
}

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