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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

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

PLoS One. 2017 Aug 23;12(8):e0183089.

PMID: 28832600

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP168021792	HPN-07		168021-79-2	Price

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