Outcomes of Peptide Vaccine GV1001 Treatment in a Murine Model of Acute Noise-Induced Hearing Loss

被引:9
作者
Lee, Sang-Yeon [1 ]
Han, Jae Joon [2 ]
Lee, Sang-Youp [3 ]
Jung, Gaon [1 ]
Min, Hyun Jin [1 ]
Song, Jae-Jin [1 ]
Koo, Ja-Won [1 ]
机构
[1] Seoul Natl Univ, Coll Med, Dept Otorhinolaryngol Head & Neck Surg, Bundang Hosp, Seongnam 463707, South Korea
[2] Soonchunhyang Univ, Coll Med, Dept Otorhinolaryngol Head & Neck Surg, Seoul Hosp, Seoul 04401, South Korea
[3] Wonkwang Univ, Sch Med, Wonkwang Univ Hosp, Dept Otolaryngol, Iksan 15865, South Korea
基金
新加坡国家研究基金会;
关键词
noise-induced hearing loss; GV1001; oxidative stress; INNER-EAR; FREE-RADICALS; MECHANISMS; INJURY; DEXAMETHASONE; CELLS;
D O I
10.3390/antiox9020112
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Noise-induced hearing loss (NIHL) is primarily caused by damage to cochlear hair cells, associated with synaptopathy. The novel cell-penetrating peptide GV1001, an antitumor agent, also has antioxidant and anti-inflammatory effects, and is otoprotective in a murine model of kanamycin-induced ototoxicity. Here, we explored whether GV1001 attenuated NIHL, and the underlying mechanism at play. We established an NIHL model by exposing 4- to 6-week-old C57/BL6 mice to white noise at 120 dB SPL for 2 h, resulting in a significant permanent threshold shift (PTS). We then subcutaneously injected saline (control), GV1001, or dexamethasone immediately after cessation of PTS-noise exposure and evaluated the threshold shifts, structural damages to outer hair cells (OHCs), and ribbon synapses. We also verified whether GV1001 attenuates oxidative stress at the level of lipid peroxidation or protein nitration in OHCs 1 h after exposure to white noise at 120 dB SPL. GV1001-treated mice exhibited significantly less hearing threshold shifts over 2 weeks and preserved OHCs and ribbon synapses compared with controls. Similarly, dexamethasone-treated mice showed comparable protection against NIHL. Importantly, GV1001 markedly attenuated oxidative stress in OHCs. Our findings suggest that GV1001 may protect against NIHL by lowering oxidative stress and may serve as preventive or adjuvant treatment.
引用
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页数:13
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