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

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.