Apelin-13 prevents apoptosis in the cochlear tissue of noise-exposed rat via Sirt-1 regulation.

Noise-induced hearing loss (NIHL) is the second most common cause of acquired hearing loss. Acoustic trauma can cause oxidative damage in the cochlear hair cells (HCs) through apoptotic pathways. Apelin is a newly discovered neuropeptide with neuroprotective effects against the oxidative stress in neurodegenerative disorder. We investigated the preventive effects of apelin-13 on the cochlear HCs and spiral ganglion neurons (SGNs) against acoustic trauma via Sirtuin-1 (Sirt-1) regulation in rats. Animals were assigned to control, control + apelin-13 (50 or 100 μg/kg, ip), and noise exposure groups without any treatment or were administered apelin-13 (50 or 100 μg/kg, ip) and EX-527 (an inhibitor of Sirt-1) prior to each noise session. In the noise groups, 110 dB white noise was applied for 6 h per 5 days. Pre- and post-exposure distortion product otoacoustic emissions (DPOAE) and cochlear superoxide dismutase (SOD) activity were assessed. Western blot evaluated the cochlear protein expressions of Sirt-1, cleaved-caspase-3, Bax, and Bcl-2. Cell apoptosis was detected through TUNEL staining. Immunofluorescence was used to examine expression of HCs and SGNs specific protein. DPOAE level were significantly improved in the noise exposure group receiving 100 μg/kg apelin-13. At high doses, apelin augmented SOD levels in the rat cochlea subjected to noise. Apelin 100 markedly increased Sirt-1, and decreased cleaved- caspase-3 expression as well as Bax/Bcl-2 ratio in the cochlea tissue of noise-exposed rats. These findings suggest the promising therapeutic potential of apelin-13 for the prevention of noise-induced injury to cochlea and hearing loss.