Direct effects of intraperilymphatic reactive oxygen species generation on cochlear function

Area of Science:

• Ototoxicity research
• Auditory neuroscience
• Reactive oxygen species (ROS) biology

Background:

• Reactive oxygen species (ROS) are implicated in ototoxicity, but their specific impact on cochlear function remains unclear.
• Understanding ROS-mediated cochlear damage is crucial for developing interventions against hearing loss.

Purpose of the Study:

• To investigate the specific effects of different ROS, including superoxide anion (O2-), hydroxyl radical (OH.), and hydrogen peroxide (H2O2), on cochlear function in guinea pigs.
• To determine the protective effects of ROS scavengers against ROS-induced ototoxicity.

Main Methods:

• Guinea pig cochleas were instilled with artificial perilymph (AP) as a control.
• Cochleas received H2O2, O2- generating system, or OH. generating system, with or without respective scavengers: catalase (CAT), superoxide dismutase (SOD), or deferoxamine (DEF).
• Compound action potential (CAP) threshold shifts and cochlear microphonic (CM) potential shifts were measured at various time points post-infusion.

Main Results:

• Instillation of O2- generating systems significantly increased high-frequency CAP threshold shifts compared to controls and the SOD/O2- group.
• H2O2 exposure resulted in significant CAP threshold shifts, which were attenuated by catalase (CAT).
• OH. generating systems caused significant CAP threshold shifts, reduced by deferoxamine (DEF), indicating ROS-specific ototoxicity.

Conclusions:

• Superoxide anion, hydroxyl radical, and H2O2 directly impair cochlear function, leading to high-frequency hearing loss.
• ROS scavengers like SOD, CAT, and DEF can mitigate ROS-induced ototoxicity.
• These findings highlight the significant role of ROS in cochlear dysfunction and suggest potential therapeutic targets for hearing loss prevention.