Metformin Protects Against Noise-Induced Hearing Loss in Male Mice.
Metformin Protects Against Noise-Induced Hearing Loss in Male Mice.
复制标题
二甲双胍可防止雄性小鼠因噪音引起的听力损失。
DOI：
10.1097/mao.0000000000004002
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发表时间：
2023-10-01
影响因子：
2.1
通讯作者：
Hertzano, Ronna
中科院分区：
文献类型：
--
作者：
Kennedy, Catherine L.;Shuster, Benjamin;Amanipour, Reza;Milon, Beatrice;Patel, Priya;Elkon, Ran;Hertzano, Ronna
Metformin treatment will protect mice from noise-induced hearing loss (NIHL). We recently identified metformin as the top-ranking, FDA-approved drug to counter inner ear molecular changes induced by permanent threshold shift (PTS)-inducing noise. This study is designed to functionally test metformin as a potential otoprotective drug against NIHL. Male and female B6CBAF1/J mice were obtained at 7–8 weeks of age. A cohort of the females underwent ovariectomy to simulate menopause and eliminate the effect of ovarian-derived estrogens. At 10 weeks of age, mice underwent a PTS-inducing noise exposure (102.5 or 105 dB SPL, 8–16 kHz, 2 hours). Auditory brainstem response (ABR) thresholds were obtained at baseline, 24 hours post noise exposure, and 1 week post noise exposure. Mice were administered metformin (200 mg/kg/day) or a saline control in their drinking water after the baseline ABR and for the remainder of the study. Following the 1-week ABR, mice were euthanized and cochlear tissue were analyzed. Metformin treatment reduced the 1-week ABR threshold shift at 16 kHz (p<0.01; d: 1.20) and 24 kHz (p<0.01; d: 1.15) as well as outer hair cell (OHC) loss in the 32–45.2 kHz range (p<0.0001; d: 2.37) in male mice. In contrast, metformin treatment did not prevent hearing loss or OHC loss in the intact or ovariectomized female mice. Metformin exhibits sex-dependent efficacy as a therapeutic for NIHL. These data compel continued investigation into metformin’s protective effects and demonstrate the importance of evaluating the therapeutic efficacy of drugs in subjects of both sexes.
