Protective Effects of Vitamin C Against Neomycin-Induced Apoptosis in HEI-OC1 Auditory Cell

Overview

Journal Neural Plast

Specialty Neurology

Date 2022 May 23

PMID 35601667

Authors

Liang Gong

Biao Chen

Jingyuan Chen

Yongxin Li

Affiliations

Soon will be listed here.

Abstract

Ototoxic hearing loss results from hair cell death via reactive oxygen species (ROS) overproduction and consequent apoptosis. We investigated the effects of vitamin C (VC) on neomycin-induced HEI-OC1 cell damage, as well as the mechanism of inhibition. HEI-OC1 cells were treated with neomycin or with vitamin C (VC). The results indicated that VC had a protective effect on neomycin-induced HEI-OC1 cell death. Mechanistically, VC decreased neomycin-induced ROS generation, suppressed cell death, and increased cell viability. VC inhibited neomycin-induced apoptosis, ameliorated neomycin reduced antiapoptotic Bcl-2 expression, and suppressed neomycin increased expression of proapoptotic Bax, caspase-3 cleavage and caspase-8. TUNEL labeling demonstrated that VC blocked neomycin-induced apoptosis. Further study revealed that the effect of VC on neomycin-induced hair cell death was through interference with JNK activation and p38 phosphorylation. These results indicate that VC via suppressed ROS generation, which inhibited cell death by counteracting apoptotic signaling induced by neomycin in cells. Hence, VC is a potential candidate for protection agent against neomycin-induced HEI-OC1 cell ototoxicity.

Citing Articles

Mechanisms and otoprotective strategies of programmed cell death on aminoglycoside-induced ototoxicity.

Han L, Wang Z, Wang D, Gao Z, Hu S, Shi D Front Cell Dev Biol. 2024; 11:1305433.

PMID: 38259515 PMC: 10800616. DOI: 10.3389/fcell.2023.1305433.

Amelioration of Sensorineural Hearing Loss through Regulation of , , and Gene Expression by a Combination of Cuscutae Semen and Rehmanniae Radix Preparata.

Hong B, Shin S, Nam Y, Shim J, Kim N, Kim M Nutrients. 2023; 15(7).

PMID: 37049613 PMC: 10097224. DOI: 10.3390/nu15071773.

Comparative neuroprotective effects of Cerebrolysin, dexamethasone, and ascorbic acid on sciatic nerve injury model: Behavioral and histopathological study.

Elhessy H, Habotta O, Eldesoqui M, Elsaed W, Soliman M, Sewilam H Front Neuroanat. 2023; 17:1090738.

PMID: 36816518 PMC: 9928760. DOI: 10.3389/fnana.2023.1090738.

References

Abi-Hachem R, Zine A, van de Water T . The injured cochlea as a target for inflammatory processes, initiation of cell death pathways and application of related otoprotectives strategies. Recent Pat CNS Drug Discov. 2010; 5(2):147-63. DOI: 10.2174/157488910791213121. View

Shin Y, Hwang H, Kang S, Chang J, Oh Y, Kim C . Inhibition of p38 mitogen-activated protein kinase ameliorates radiation-induced ototoxicity in zebrafish and cochlea-derived cell lines. Neurotoxicology. 2013; 40:111-22. DOI: 10.1016/j.neuro.2013.12.006. View

Elmore S . Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007; 35(4):495-516. PMC: 2117903. DOI: 10.1080/01926230701320337. View

Pirvola U, Virkkala J, Saarma M, Murakata C, Camoratto A, Walton K . Rescue of hearing, auditory hair cells, and neurons by CEP-1347/KT7515, an inhibitor of c-Jun N-terminal kinase activation. J Neurosci. 2000; 20(1):43-50. PMC: 6774096. View

Finkel T . Oxygen radicals and signaling. Curr Opin Cell Biol. 1998; 10(2):248-53. DOI: 10.1016/s0955-0674(98)80147-6. View

Conlon B, Aran J, Erre J, Smith D . Attenuation of aminoglycoside-induced cochlear damage with the metabolic antioxidant alpha-lipoic acid. Hear Res. 1999; 128(1-2):40-4. DOI: 10.1016/s0378-5955(98)00195-6. View

Chen F, Hill K, Guan Y, Schacht J, Sha S . Activation of apoptotic pathways in the absence of cell death in an inner-ear immortomouse cell line. Hear Res. 2012; 284(1-2):33-41. PMC: 3289757. DOI: 10.1016/j.heares.2011.12.007. View

Blackwell D, Lucas J, Clarke T . Summary health statistics for U.S. adults: national health interview survey, 2012. Vital Health Stat 10. 2014; (260):1-161. View

Padayatty S, Levine M . Vitamin C: the known and the unknown and Goldilocks. Oral Dis. 2016; 22(6):463-93. PMC: 4959991. DOI: 10.1111/odi.12446. View

10.

Genestra M . Oxyl radicals, redox-sensitive signalling cascades and antioxidants. Cell Signal. 2007; 19(9):1807-19. DOI: 10.1016/j.cellsig.2007.04.009. View

11.

Ibrahim I, Zeitouni A, da Silva S . Effect of Antioxidant Vitamins as Adjuvant Therapy for Sudden Sensorineural Hearing Loss: Systematic Review Study. Audiol Neurootol. 2018; 23(1):1-7. DOI: 10.1159/000486274. View

12.

Zhao J, Liu H, Huang Z, Yang R, Gong L . The Ameliorative Effect of JNK Inhibitor D-JNKI-1 on Neomycin-Induced Apoptosis in HEI-OC1 Cells. Front Mol Neurosci. 2022; 15:824762. PMC: 8963355. DOI: 10.3389/fnmol.2022.824762. View

13.

Maruyama J, Yamagata T, Ulfendahl M, Bredberg G, Altschuler R, Miller J . Effects of antioxidants on auditory nerve function and survival in deafened guinea pigs. Neurobiol Dis. 2006; 25(2):309-18. PMC: 2048572. DOI: 10.1016/j.nbd.2006.09.012. View

14.

Tabuchi K, Oikawa K, Hoshino T, Nishimura B, Hayashi K, Yanagawa T . Cochlear protection from acoustic injury by inhibitors of p38 mitogen-activated protein kinase and sequestosome 1 stress protein. Neuroscience. 2009; 166(2):665-70. DOI: 10.1016/j.neuroscience.2009.12.038. View

15.

Kalinec G, Park C, Thein P, Kalinec F . Working with Auditory HEI-OC1 Cells. J Vis Exp. 2016; (115). PMC: 5091972. DOI: 10.3791/54425. View

16.

McFadden S, Woo J, Michalak N, Ding D . Dietary vitamin C supplementation reduces noise-induced hearing loss in guinea pigs. Hear Res. 2005; 202(1-2):200-8. DOI: 10.1016/j.heares.2004.10.011. View

17.

Zhou J, Chen C, Chen X, Fei Y, Jiang L, Wang G . Vitamin C Promotes Apoptosis and Cell Cycle Arrest in Oral Squamous Cell Carcinoma. Front Oncol. 2020; 10:976. PMC: 7298137. DOI: 10.3389/fonc.2020.00976. View

18.

Lo Y, Wong J, Cruz T . Reactive oxygen species mediate cytokine activation of c-Jun NH2-terminal kinases. J Biol Chem. 1996; 271(26):15703-7. DOI: 10.1074/jbc.271.26.15703. View

19.

Huang T, Cheng A, Stupak H, Liu W, Kim A, Staecker H . Oxidative stress-induced apoptosis of cochlear sensory cells: otoprotective strategies. Int J Dev Neurosci. 2000; 18(2-3):259-70. DOI: 10.1016/s0736-5748(99)00094-5. View

20.

Cunningham L, Cheng A, Rubel E . Caspase activation in hair cells of the mouse utricle exposed to neomycin. J Neurosci. 2002; 22(19):8532-40. PMC: 6757801. View