دورية أكاديمية
Multifunctional redox modulator prevents blast-induced loss of cochlear and vestibular hair cells and auditory spiral ganglion neurons.
العنوان: | Multifunctional redox modulator prevents blast-induced loss of cochlear and vestibular hair cells and auditory spiral ganglion neurons. |
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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).) |
References: | Hear Res. 2020 Oct;396:108073. (PMID: 32956992) Am J Ind Med. 2005 Dec;48(6):446-58. (PMID: 16299704) Brain Inj. 2017;31(9):1188-1194. (PMID: 28981340) Am J Audiol. 2011 Jun;20(1):33-41. (PMID: 21474555) Proc Natl Acad Sci U S A. 2018 May 22;115(21):E4853-E4860. (PMID: 29735658) Noise Health. 2018 May-Jun;20(94):112-119. (PMID: 29785976) J Neurophysiol. 2011 Dec;106(6):2950-63. (PMID: 21918003) Korean J Audiol. 2012 Dec;16(3):103-7. (PMID: 24653882) Sci Rep. 2020 Jan 30;10(1):1478. (PMID: 32001745) Int Immunopharmacol. 2021 Jun;95:107576. (PMID: 33770730) Hear Res. 1984 Mar;13(3):229-47. (PMID: 6735931) FASEB J. 2013 Sep;27(9):3730-40. (PMID: 23729595) MMWR Morb Mortal Wkly Rep. 2017 Feb 10;66(5):139-144. (PMID: 28182600) Eur J Neurosci. 2005 Feb;21(3):637-46. (PMID: 15733082) PLoS One. 2013 Jul 01;8(7):e67618. (PMID: 23840874) Hear Res. 1992 Oct;62(2):217-36. (PMID: 1429265) Hear Res. 2003 Jul;181(1-2):65-72. (PMID: 12855364) Eur Arch Otorhinolaryngol. 2017 Apr;274(4):1821-1834. (PMID: 27858145) Neurosci Lett. 2005 Jun 3;380(3):234-8. (PMID: 15862892) J Neurotrauma. 2016 Jan 1;33(1):71-81. (PMID: 25790248) Hear Res. 2017 Feb;344:158-169. (PMID: 27890677) Hear Res. 2021 Feb;400:108125. (PMID: 33302057) Hear Res. 2013 Sep;303:30-8. (PMID: 23422312) Otol Neurotol. 2003 May;24(3):409-17. (PMID: 12806293) Hear Res. 2012 Mar;285(1-2):29-39. (PMID: 22326291) Adv Otorhinolaryngol. 2001;58:98-109. (PMID: 11885558) Neurotox Res. 2012 Aug;22(2):158-69. (PMID: 22476946) Hear Res. 2013 Jan;295:150-60. (PMID: 22728305) Brain Res. 2007 May 7;1148:83-9. (PMID: 17359945) Can J Neurol Sci. 2020 May;47(3):289-300. (PMID: 32029015) J Assoc Res Otolaryngol. 2016 Aug;17(4):289-302. (PMID: 27095478) Exp Neurol. 2016 Sep;283(Pt A):16-28. (PMID: 27246999) J Neurosci. 2015 May 13;35(19):7509-20. (PMID: 25972177) J Audiol Otol. 2015 Dec;19(3):111-9. (PMID: 26771008) Noise Health. 2020 Oct-Dec;22(107):90-98. (PMID: 33402609) Hear Res. 1991 Feb;51(2):247-54. (PMID: 2032960) J Neurosci. 2012 Jan 11;32(2):405-10. (PMID: 22238076) Hear Res. 2020 Sep 15;395:108022. (PMID: 32663733) Hear Res. 2022 Feb;414:108409. (PMID: 34953289) Front Cell Dev Biol. 2021 May 24;9:643709. (PMID: 34109172) Am J Otol. 2000 Jul;21(4):505-9. (PMID: 10912695) J Neurosci Methods. 2015 Mar 15;242:82-92. (PMID: 25597910) J Comp Neurol. 2011 Jun 1;519(8):1526-45. (PMID: 21452221) Hear Res. 1986;23(1):93-104. (PMID: 3488306) Acta Otolaryngol Suppl. 2006 Dec;(556):54-8. (PMID: 17114144) Front Neurol. 2018 May 14;9:297. (PMID: 29867715) Aging (Albany NY). 2016 Apr;8(4):730-50. (PMID: 26977590) Eur Arch Otorhinolaryngol. 2021 Oct;278(10):3773-3776. (PMID: 33169181) Ann Otol Rhinol Laryngol Suppl. 1989 May;140:23-34. (PMID: 2497695) J Neurosci. 2013 Aug 7;33(32):13042-52. (PMID: 23926258) J Neuroinflammation. 2011 Jan 24;8(1):7. (PMID: 21261959) Hear Res. 2021 Aug;407:108292. (PMID: 34214947) J Neurosci. 2000 Dec 1;20(23):8750-3. (PMID: 11102482) Hear Res. 1994 Apr;74(1-2):204-16. (PMID: 8040089) J Med Chem. 2015 Nov 25;58(22):8796-805. (PMID: 26068053) Brain Res. 2004 Sep 3;1019(1-2):201-9. (PMID: 15306254) Otol Neurotol. 2002 Nov;23(6):953-7. (PMID: 12438862) Toxicol Lett. 2016 Mar 14;245:78-85. (PMID: 26778349) Neuroscience. 2010 Jun 2;167(4):1216-26. (PMID: 20206235) J Neurosci. 1994 Oct;14(10):6058-70. (PMID: 7931562) Acta Otolaryngol Suppl. 1995;519:87-92. (PMID: 7610900) Am J Audiol. 2016 Dec 01;25(4):359-363. (PMID: 27768802) J Acoust Soc Am. 2019 Nov;146(5):4020. (PMID: 31795714) EXS. 1992;62:99-108. (PMID: 1450609) Ear Hear. 2006 Feb;27(1):1-19. (PMID: 16446561) Brain Res Brain Res Rev. 2003 Sep;43(1):17-28. (PMID: 14499459) Antioxid Redox Signal. 2021 Aug 13;:. (PMID: 34162214) J Assoc Res Otolaryngol. 2002 Mar;3(1):68-79. (PMID: 12083725) J Int Adv Otol. 2016 Apr;12(1):101-5. (PMID: 27340993) Int Arch Occup Environ Health. 2021 Oct;94(7):1703-1707. (PMID: 34389884) Hear Res. 2020 Mar 15;388:107880. (PMID: 31945692) Hear Res. 2000 Dec;150(1-2):245-57. (PMID: 11077207) |
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 |
تدمد: | 2045-2322 |
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DOI: | 10.1038/s41598-024-66406-1 |