Department of Otorhinolaryngology-Head & Neck Surgery, CHA University College of Medicine, Republic of Korea.
Department of Otorhinolaryngology-Head & Neck Surgery, Seoul National University Bundang Hospital, Republic of Korea.
Neurosci Lett. 2020 Mar 23;722:134838. doi: 10.1016/j.neulet.2020.134838. Epub 2020 Feb 12.
Tauroursodeoxycholic acid (TUDCA) has been reported to be protective against apoptosis and oxidative stress in various cell types. A few studies have demonstrated otoprotective effects of TUDCA in mouse models. This study investigated the otoprotective effects of TUDCA in cisplatin (CXP)-induced hearing-loss rats. Eight-week-old female Sprague-Dawley rats were used. The CXP group received intraperitoneal injection of CXP at a dose of 5 mg/kg from day 1 to day 3. The CXP + TUDCA group received an intraperitoneal injection of 5 mg/kg CXP and 100 mg/kg TUDCA from day 1 to day 3. The mRNA expression levels of heme oxygenase 1 (HO1) and superoxide dismutase 2 (SOD2) were measured, and the protein levels of caspase 3, cleaved caspase 3, and aryl hydrocarbon receptor (AhR) were evaluated. The CXP group demonstrated higher mean auditory brainstem responses (ABR) thresholds than the control group. The mean ABR threshold shifts were lower in the CXP + TUDCA group than in the CXP group. The CXP group showed elevated HO1 and SOD2 mRNA expression levels compared to the control group, but these changes were reversed in the CXP + TUDCA group. Compared to the levels in the control group, caspase 3, cleaved caspase 3, and AhR levels were higher in the CXP group, but the increase in cleaved caspase-3 was attenuated in the CXP + TUDCA group. The cochlea showed a higher number of spiral ganglion cells and outer hair cells in the CXP + TUDCA group than in the CXP group. TUDCA reduced CXP-induced hearing loss in adult rats. The HO1-mediated antioxidative effects attenuated apoptosis in the cochlea, but AhR activation was not reversed.
牛磺熊脱氧胆酸（TUDCA）已被报道在各种细胞类型中具有抗细胞凋亡和氧化应激的作用。一些研究表明 TUDCA 在小鼠模型中具有耳保护作用。本研究探讨了 TUDCA 在顺铂（CXP）诱导的听力损失大鼠中的耳保护作用。使用 8 周龄雌性 Sprague-Dawley 大鼠。CXP 组从第 1 天到第 3 天每天腹腔注射 5mg/kg 的 CXP。CXP+TUDCA 组从第 1 天到第 3 天每天腹腔注射 5mg/kg 的 CXP 和 100mg/kg 的 TUDCA。测量血红素加氧酶 1（HO1）和超氧化物歧化酶 2（SOD2）的 mRNA 表达水平，并评估半胱天冬酶 3、切割的半胱天冬酶 3 和芳香烃受体（AhR）的蛋白水平。CXP 组的平均听性脑干反应（ABR）阈值高于对照组。CXP+TUDCA 组的平均 ABR 阈值变化低于 CXP 组。与对照组相比，CXP 组的 HO1 和 SOD2 mRNA 表达水平升高，但 CXP+TUDCA 组的这些变化得到了逆转。与对照组相比，CXP 组的 caspase 3、切割的 caspase 3 和 AhR 水平升高，但 CXP+TUDCA 组的切割的 caspase-3 增加被减弱。与 CXP 组相比，CXP+TUDCA 组的耳蜗螺旋神经节细胞和外毛细胞数量更多。TUDCA 减轻了成年大鼠的 CXP 诱导的听力损失。HO1 介导的抗氧化作用减轻了耳蜗中的细胞凋亡，但 AhR 激活未得到逆转。
