Intracellular oxidative stress pathways and antioxidant systems in cochlear cells

Intracellular oxidative stress pathways and antioxidant systems in cochlear cells encompass the biochemical networks responsible for maintaining redox homeostasis in the inner ear. These systems are critical for protecting sensitive auditory structures, such as the organ of Corti and spiral ganglion neurons, from damage caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) (Henderson et al., 2006, PubMed: 16631331). Key components include the pro-oxidant enzyme NADPH oxidase 3 (NOX3), which is uniquely highly expressed in the cochlea, and the antioxidant response element (ARE) regulated by the transcription factor Nrf2 (Ryter et al., 2007, PubMed: 17261490). Excessive ROS generation, triggered by loud noise, aging, or ototoxic medications like cisplatin and aminoglycosides, overwhelms these endogenous defenses, leading to lipid peroxidation and hair cell apoptosis (Schacht et al., 2012, PubMed: 22554771). Therapeutic interventions aim to bolster these systems using exogenous antioxidants like N-acetylcysteine or glutathione peroxidase mimics like ebselen (Kil et al., 2017, PubMed: 28641068). Sodium thiosulfate has also been approved to reduce the risk of cisplatin-induced ototoxicity by neutralizing platinum-induced oxidative stress (Freyer et al., 2018, PubMed: 30035650). Understanding these pathways is essential for developing otoprotective strategies to prevent permanent sensorineural hearing loss.

Other names

Cochlear antioxidant defense systemCochlear redox signaling pathwaysInner ear oxidative stress responseCochlear ROS/RNS pathways

Neutralization of reactive oxygen species (ROS), induction of endogenous antioxidant enzymes via Nrf2 activation, and inhibition of pro-oxidant enzymes like NOX3.