The SIRT2 inhibitor AK-7 decreases cochlear cell apoptosis and attenuates noise-induced hearing loss

Area of Science:

• Oto-neurology
• Cellular Biology
• Molecular Medicine

Background:

• Oxidative damage is a key factor in cochlear cell apoptosis and noise-induced hearing loss (NIHL).
• Sirtuin 2 (SIRT2), an NAD-dependent deacetylase, regulates cellular oxidative stress responses, but its role in NIHL is unclear.

Purpose of the Study:

• To investigate the role of SIRT2 in NIHL.
• To evaluate the therapeutic potential of SIRT2 inhibition using AK-7 in NIHL.

Main Methods:

• Assessed SIRT2 expression in cochlear tissue following noise exposure.
• Administered AK-7, a SIRT2 inhibitor, to mice exposed to noise.
• Evaluated levels of oxidative DNA damage and apoptosis in cochlear cells.
• Tested the effect of AK-7 on oxidative stress-induced apoptosis in mouse inner ear HEI-OC1 cells in vitro.

Main Results:

• SIRT2 was found to be upregulated in the cochlea after noise exposure.
• AK-7 treatment attenuated the progression of NIHL.
• AK-7 significantly reduced oxidative nuclear DNA damage and apoptosis in the cochlea post-noise exposure.
• AK-7 decreased apoptosis in mouse inner ear cells subjected to oxidative stress in vitro.

Conclusions:

• SIRT2 inhibition by AK-7 mitigates cochlear cell apoptosis and oxidative damage, offering protection against NIHL.
• AK-7 demonstrates potential as a therapeutic agent for preventing or treating noise-induced hearing loss.