Abstract
Sensorineural hearing loss (SNHL) is one of the most common causes of disability worldwide. Previous evidence suggests that reactive oxygen species (ROS) may play an important role in the occurrence and development of SNHL, while its mechanism remains unclear. We cultured dissected organs of Corti in medium containing different concentrations (0, 0.25, 0.5, 0.75, 1, and 1.25 mM) of hydrogen peroxide (H2O2) and established a four-concentration model of 0, 0.5, 0.75, and 1 mM to study different degrees of damage. We examined ROS-induced mitochondrial damage and the role of sirtuin 3 (SIRT3). Our results revealed that the number of ribbon synapses and hair cells appeared significantly concentration-dependent decrease with exposure to H2O2. Outer hair cells (OHCs) and inner hair cells (IHCs) began to be lost, and activation of apoptosis of hair cells (HCs) was observed at 0.75 mM and 1 mM H2O2, respectively. In contrast with the control group, the accumulation of ROS was significantly higher, and the mitochondrial membrane potential (MMP) was lower in the H2O2-treated groups. Furthermore, the expression of SIRT3, FOXO3A, and SOD2 proteins declined, except for an initial elevation of SIRT3 between 0 and 0.75 mM H2O2. Administration of the selective SIRT3 inhibitor 3-(1H-1,2,3-triazol-4-yl) pyridine resulted in increased damage to the cochlea, including loss of ribbon synapses and hair cells, apoptosis of hair cells, more production of ROS, and reduced mitochondrial membrane potential. Thoroughly, our results highlight that ROS-induced mitochondrial oxidative damage drives hair cell degeneration and apoptosis. Furthermore, SIRT3 is crucial for preserving mitochondrial function and protecting the cochlea from oxidative damage and may represent a possible therapeutic target for SNHL.
Highlights
As life expectancy increases, sensorineural hearing loss has become more common, affecting people’s living quality [1]
Our findings showed that after a 24 h exposure to H2O2, the number of ribbon synapses and cochlear hair cells was significantly decreased in a concentration-dependent manner
Our findings indicated that H2O2 resulted in a concentrationdependent decrease in mitochondrial membrane potential, and sirtuin 3 (SIRT3) played an important role in protecting mitochondrial function
Summary
Sensorineural hearing loss has become more common, affecting people’s living quality [1]. ARHL or presbycusis is a progressive decline in hearing function that is the most prevalent type of SNHL in the elderly [2,3,4,5], which is characterized by higher hearing thresholds, beginning at high frequencies and spreading toward low frequencies, accompanied by the loss of HCs and spiral ganglion neurons (SGNs) from the basal to apical turn. Noise-induced hearing loss (NIHL) is the second most prevalent type of SNHL, behind presbycusis [3] It is typically characterized by elevation in hearing thresholds and speech perception, tinnitus, and auditory processing disorders [6] due to damage to and/or death of cochlear hair cells, as well as primary auditory neurons after exposure to strong noise stimulation [7]. Platinum-based anticancer drugs and aminoglycoside antibiotics can lead to hearing loss at high frequencies and preferential damage to OHCs at the cochlea basal turn [8,9,10]
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