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

Journal Article · · Scientific Reports
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

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.

Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
USDOE Office of Science (SC), Basic Energy Sciences (BES); US Department of the Navy, Office of Naval Research (ONR)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1481415
Journal Information:
Scientific Reports, Vol. 8, Issue 1; ISSN 2045-2322
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 16 works
Citation information provided by
Web of Science

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Identifying components of the hair-cell interactome involved in cochlear amplification journal January 2009
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Cited By (3)

Synthesis of deuterium-labeled (3R, 5S)-fluvastatin and (3S, 5R)-fluvastatin journal October 2018
Evidence Supporting the Hypothesis That Inflammation-Induced Vasospasm Is Involved in the Pathogenesis of Acquired Sensorineural Hearing Loss journal November 2019
Visualizing the 3D cytoarchitecture of the human cochlea in an intact temporal bone using synchrotron radiation phase contrast imaging journal January 2018

Figures / Tables (5)


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