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

Donald Ewert; Ning Hu; Xiaoping Du; Wei Li; Matthew B West; Chul-Hee Choi; Robert Floyd; Richard D Kopke

doi:10.1371/journal.pone.0183089

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

Journal article

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Peer reviewed

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

Donald Ewert, Ning Hu, Xiaoping Du, Wei Li, Matthew B West, Chul-Hee Choi, Robert Floyd and Richard D Kopke

PloS one, Vol.12(8), pp.e0183089-e0183089

08/23/2017

DOI: 10.1371/journal.pone.0183089

PMCID: PMC5568441

PMID: 28832600

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Abstract

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.

Action Potentials

Acute Disease

Animals

Benzenesulfonates - pharmacology

Chinchilla

Cochlea - drug effects

Cochlea - injuries

Cochlea - physiopathology

Female

Free Radical Scavengers - pharmacology

Wounds and Injuries - pathology

Wounds and Injuries - physiopathology

Details

Title: Subtitle: HPN-07, a free radical spin trapping agent, protects against functional, cellular and electrophysiological changes in the cochlea induced by acute acoustic trauma
Creators: Donald Ewert - Hough Ear Institute
Ning Hu - University of Iowa
Xiaoping Du - Hough Ear Institute
Wei Li - Hough Ear Institute
Matthew B West - Hough Ear Institute
Chul-Hee Choi - Catholic University of Daegu
Robert Floyd - Oklahoma Medical Research Foundation
Richard D Kopke - Hough Ear Institute
Resource Type: Journal article
Publication Details: PloS one, Vol.12(8), pp.e0183089-e0183089
DOI: 10.1371/journal.pone.0183089
PMID: 28832600
PMCID: PMC5568441
ISSN: 1932-6203
eISSN: 1932-6203
Language: English
Date published: 08/23/2017
Academic Unit: Biology
Record Identifier: 9984627336802771

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