Fluvastatin protects cochleae from damage by high-level noise

Richter, Claus-Peter; Young, Hunter; Richter, Sonja V.; Smith-Bronstein, Virginia; Stock, Stuart R.; Xiao, Xianghui; Soriano, Carmen; Whitlon, Donna S.

doi:10.1038/s41598-018-21336-7

Fluvastatin protects cochleae from damage by high-level noise

Journal Article · Wed Feb 14 00:00:00 EST 2018 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-018-21336-7· OSTI ID:1481415

^[1]; Young, Hunter ^[2]; Richter, Sonja V. ^[2]; Smith-Bronstein, Virginia ^[2]; Stock, Stuart R. ^[3]; Xiao, Xianghui ^[4]; Soriano, Carmen ^[4]; Whitlon, Donna S. ^[5]

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
Northwestern University Feinberg School of Medicine, Chicago, IL (United States). Department of Otolaryngology
Northwestern University Feinberg School of Medicine, Chicago, IL (United States). Department of Cell and Molecular Biology
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
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.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: Office of Naval Research; USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 1481415

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 8; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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