Dexamethasone treatment of murine auditory hair cells and cochlear explants attenuates tumor necrosis factor-[alpha]-initiated apoptotic damage

• Published in: PloS one 2023-09, Vol.18 (9), p.e0291780
• Main Authors: Kang, Byung Chul, Yi, Junyeong, Kim, Song Hee, Pak, Jhang Ho, Chung, Jong Woo
• Format: Article
• Language: English
• Subjects: Apoptosis; Care and treatment; Causes of; Central nervous system depressants; Complications and side effects; Dexamethasone; Hearing loss; Necrosis; Patient outcomes; Tumor necrosis factor; Tumors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0291780

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.