PMID- 37733709 OWN - NLM STAT- MEDLINE DCOM- 20230925 LR - 20230926 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 18 IP - 9 DP - 2023 TI - Dexamethasone treatment of murine auditory hair cells and cochlear explants attenuates tumor necrosis factor-alpha-initiated apoptotic damage. PG - e0291780 LID - 10.1371/journal.pone.0291780 [doi] LID - e0291780 AB - The most common cause of sensorineural hearing loss is damage of auditory hair cells. Tumor necrosis factor-alpha (TNF-alpha) is closely associated with sensorineural hearing loss. The present study examined the preconditioning effect of dexamethasone (DEX) on TNF-alpha-induced ototoxicity in mouse auditory hair cells (HEI-OC1) and cochlear explants. Treatment of HEI-OC1 with 10 ng/ml TNF-alpha for 24 h decreased cell viability, increased the accumulation of reactive oxygen species (ROS), and induced caspase-mediated apoptotic signaling pathways. Pretreatment with 10 nM DEX for 6 h before TNF-alpha exposure restored cell viability, decreased ROS accumulation, and attenuated apoptotic signaling activation induced by TNF-alpha. Incubation of cochlear explants with 20 ng/ml TNF-alpha for 24 h resulted in significant loss of both inner hair cells (IHCs) and outer hair cells (OHCs) and an increase in apoptotic activation accessed by annexin V staining. The cochlear explants pre-incubated with 10 nM DEX attenuated TNF-alpha ototoxicity in both IHCs and OHCs and apoptotic cell death. These results indicated that DEX plays a protective role in ototoxicity induced by TNF-alpha through attenuation of caspase-dependent apoptosis signaling pathway and ROS accumulation. CI - Copyright: (c) 2023 Kang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. FAU - Kang, Byung Chul AU - Kang BC AUID- ORCID: 0000-0002-5536-7796 AD - Department of Otorhinolaryngology-Head and Neck Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea. FAU - Yi, Junyeong AU - Yi J AD - Department of Otorhinolaryngology-Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. FAU - Kim, Song Hee AU - Kim SH AD - Department of Otorhinolaryngology-Head and Neck Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea. FAU - Pak, Jhang Ho AU - Pak JH AUID- ORCID: 0000-0001-5104-5995 AD - Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea. FAU - Chung, Jong Woo AU - Chung JW AUID- ORCID: 0000-0003-0765-9134 AD - Department of Otorhinolaryngology-Head and Neck Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20230921 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Reactive Oxygen Species) RN - 7S5I7G3JQL (Dexamethasone) SB - IM MH - Animals MH - Mice MH - Tumor Necrosis Factor-alpha MH - *Ototoxicity MH - Reactive Oxygen Species MH - Hair Cells, Auditory, Outer MH - *Hearing Loss, Sensorineural MH - Dexamethasone/pharmacology PMC - PMC10513268 COIS- The authors have declared that no competing interests exist. EDAT- 2023/09/21 18:42 MHDA- 2023/09/25 06:42 PMCR- 2023/09/21 CRDT- 2023/09/21 13:43 PHST- 2023/06/19 00:00 [received] PHST- 2023/09/05 00:00 [accepted] PHST- 2023/09/25 06:42 [medline] PHST- 2023/09/21 18:42 [pubmed] PHST- 2023/09/21 13:43 [entrez] PHST- 2023/09/21 00:00 [pmc-release] AID - PONE-D-23-19102 [pii] AID - 10.1371/journal.pone.0291780 [doi] PST - epublish SO - PLoS One. 2023 Sep 21;18(9):e0291780. doi: 10.1371/journal.pone.0291780. eCollection 2023.