دورية أكاديمية
أعرض في EDS

Multifunctional redox modulator prevents blast-induced loss of cochlear and vestibular hair cells and auditory spiral ganglion neurons.

التفاصيل البيبلوغرافية
العنوان: Multifunctional redox modulator prevents blast-induced loss of cochlear and vestibular hair cells and auditory spiral ganglion neurons.
المؤلفون: Ding D; Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, 14214, USA., Manohar S; Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, 14214, USA., Kador PF; Therapeutic Vision, Inc., Omaha, NE, 68164, USA., Salvi R; Center for Hearing and Deafness, University at Buffalo, Buffalo, NY, 14214, USA. salvi@buffalo.edu.
المصدر: Scientific reports [Sci Rep] 2024 Jul 03; Vol. 14 (1), pp. 15296. Date of Electronic Publication: 2024 Jul 03.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: Spiral Ganglion*/drug effects , Spiral Ganglion*/pathology , Blast Injuries*/prevention & control , Hair Cells, Vestibular*/drug effects , Hair Cells, Vestibular*/metabolism, Animals ; Rats ; Male ; Oxidation-Reduction ; Rats, Sprague-Dawley ; Cochlea/drug effects ; Cochlea/pathology ; Hair Cells, Auditory/drug effects ; Hair Cells, Auditory/pathology ; Oxidative Stress/drug effects ; Hearing Loss, Noise-Induced/prevention & control ; Hearing Loss, Noise-Induced/pathology
مستخلص: Blast wave exposure, a leading cause of hearing loss and balance dysfunction among military personnel, arises primarily from direct mechanical damage to the mechanosensory hair cells and supporting structures or indirectly through excessive oxidative stress. We previously reported that HK-2, an orally active, multifunctional redox modulator (MFRM), was highly effective in reducing both hearing loss and hair cells loss in rats exposed to a moderate intensity workday noise that likely damages the cochlea primarily from oxidative stress versus direct mechanical trauma. To determine if HK-2 could also protect cochlear and vestibular cells from damage caused primarily from direct blast-induced mechanical trauma versus oxidative stress, we exposed rats to six blasts of 186 dB peak SPL. The rats were divided into four groups: (B) blast alone, (BEP) blast plus earplugs, (BHK-2) blast plus HK-2 and (BEPHK-2) blast plus earplugs plus HK-2. HK-2 was orally administered at 50 mg/kg/d from 7-days before to 30-day after the blast exposure. Cochlear and vestibular tissues were harvested 60-d post-exposure and evaluated for loss of outer hair cells (OHC), inner hair cells (IHC), auditory nerve fibers (ANF), spiral ganglion neurons (SGN) and vestibular hair cells in the saccule, utricle and semicircular canals. In the untreated blast-exposed group (B), massive losses occurred to OHC, IHC, ANF, SGN and only the vestibular hair cells in the striola region of the saccule. In contrast, rats treated with HK-2 (BHK-2) sustained significantly less OHC (67%) and IHC (57%) loss compared to the B group. OHC and IHC losses were smallest in the BEPHK-2 group, but not significantly different from the BEP group indicating lack of protective synergy between EP and HK-2. There was no loss of ANF, SGN or saccular hair cells in the BHK-2, BEP and BEPHK-2 groups. Thus, HK-2 not only significantly reduced OHC and IHC damage, but completely prevented loss of ANF, SGN and saccule hair cells. The powerful protective effects of this oral MFRM make HK-2 an extremely promising candidate for human clinical trials.
(© 2024. The Author(s).)
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معلومات مُعتمدة: R43 DC020687 United States DC NIDCD NIH HHS
تواريخ الأحداث: Date Created: 20240703 Date Completed: 20240703 Latest Revision: 20240716
رمز التحديث: 20240716
مُعرف محوري في PubMed: PMC11222375
DOI: 10.1038/s41598-024-66406-1
PMID: 38961203
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/s41598-024-66406-1