HPN-07, a free radical spin trapping agent, protects against functional, cellular and electrophysiological changes in the cochlea induced by acute acoustic trauma

Oxidative stress is considered a major cause of the structural and functional changes associated with auditory pathologies induced by exposure to acute acoustic trauma AAT). In the present study, we examined the otoprotective effects of 2,4-disulfophenyl-N-tert-butylnitrone (HPN-07), a nitrone-based...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2017-08, Vol.12 (8), p.e0183089-e0183089
Main Authors: Ewert, Donald, Hu, Ning, Du, Xiaoping, Li, Wei, West, Matthew B, Choi, Chul-Hee, Floyd, Robert, Kopke, Richard D
Format: Article
Language:English
Subjects:
Acoustic measurement
Acoustic noise
Acoustics
Action Potentials
Acute Disease
Animals
Auditory system
Benzenesulfonates - pharmacology
Biological effects
Biological models (mathematics)
Biology and Life Sciences
Brain research
Brain stem
Calretinin
Care and treatment
Chinchilla
Cochlea
Cochlea - drug effects
Cochlea - injuries
Cochlea - physiopathology
Engineering and Technology
Evoked potentials
Exposure
Female
Fibers
Free Radical Scavengers - pharmacology
Free radicals
Gene expression
Hair
Hearing loss
Hearing protection
Homeostasis
Intervention
Medical research
Medicine and Health Sciences
Molecular biology
Noise
Noise levels
Otoacoustic emissions
Otology
Ototoxicity
Oxidative stress
Physiology
Recovery of function
Sensory neurons
Structure-function relationships
Studies
Trauma
Wounds and Injuries - pathology
Wounds and Injuries - physiopathology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Oxidative stress is considered a major cause of the structural and functional changes associated with auditory pathologies induced by exposure to acute acoustic trauma AAT). In the present study, we examined the otoprotective effects of 2,4-disulfophenyl-N-tert-butylnitrone (HPN-07), a nitrone-based free radical trap, on the physiological and cellular changes in the auditory system of chinchilla following a six-hour exposure to 4 kHz octave band noise at 105 dB SPL. HPN-07 has been shown to suppress oxidative stress in biological models of a variety of disorders. Our results show that administration of HPN-07 beginning four hours after acoustic trauma accelerated and enhanced auditory/cochlear functional recovery, as measured by auditory brainstem responses (ABR), distortion product otoacoustic emissions (DPOAE), compound action potentials (CAP), and cochlear microphonics (CM). The normally tight correlation between the endocochlear potential (EP) and evoked potentials of CAP and CM were persistently disrupted after noise trauma in untreated animals but returned to homeostatic conditions in HPN-07 treated animals. Histological analyses revealed several therapeutic advantages associated with HPN-07 treatment following AAT, including reductions in inner and outer hair cell loss; reductions in AAT-induced loss of calretinin-positive afferent nerve fibers in the spiral lamina; and reductions in fibrocyte loss within the spiral ligament. These findings support the conclusion that early intervention with HPN-07 following an AAT efficiently blocks the propagative ototoxic effects of oxidative stress, thereby preserving the homeostatic and functional integrity of the cochlea.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0183089