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Evaluating the Efficacy of Taurodeoxycholic Acid in Providing Otoprotection Using an in vitro Model of Electrode Insertion Trauma.
Frontiers in Molecular Neuroscience ( IF 4.8 ) Pub Date : 2020-06-02 , DOI: 10.3389/fnmol.2020.00113
Viraj Shah 1 , Rahul Mittal 1 , David Shahal 1 , Priyanka Sinha 1 , Erdogan Bulut 1 , Jeenu Mittal 1 , Adrien A Eshraghi 1, 2, 3
Affiliation  

Cochlear implants (CIs) are widely used to provide auditory rehabilitation to individuals having severe to profound sensorineural hearing loss (SNHL). However, insertion of electrode leads to inner trauma and activation of inflammatory and apoptotic signaling cascades resulting in loss of residual hearing in implanted individuals. Pharmaceutical interventions that can target these signaling cascades hold great potential for preserving residual hearing by preventing sensory cell damage. Bile salts have shown efficacy in various regions of the body as powerful antioxidants and anti-inflammatory agents. However, their efficacy against inner ear trauma has never been explored. The objective of this study was to determine whether taurodeoxycholic acid (TDCA), a bile salt derivative, can prevent sensory cell damage employing an in vitro model of electrode insertion trauma (EIT). The organ of Corti (OC) explants were dissected from postnatal day 3 (P-3) rats and placed in serum-free media. Explants were divided into control and experimental groups: (1) untreated controls; (2) EIT; (3) EIT+ TDCA (different concentrations). Hair cell (HC) density, analyses of apoptosis pathway (cleaved caspase 3), levels of reactive oxygen species (ROS) as well as inducible nitric oxide synthase (iNOS) activity and Mitochondrial Membrane Potential (MMP) were assayed. Treatment with TDCA provided significant otoprotection against HC loss in a dose-dependent manner. The molecular mechanisms underlying otoprotection involved decreasing oxidative stress, lowering levels of iNOS, and abrogating generation of cleaved caspase 3. The results of the present study suggest that TDCA provides efficient otoprotection against EIT, in vitro and should be explored for developing pharmaceutical interventions to preserve residual hearing post-cochlear implantation.



中文翻译:

使用电极插入创伤的体外模型评估牛磺脱氧胆酸在提供耳保护作用中的功效。

人工耳蜗(CIs)广泛用于为患有严重至严重的感音神经性听力丧失(SNHL)的个人提供听觉康复。然而,电极的插入导致内部创伤以及炎症和凋亡信号级联反应的激活,导致植入个体的残余听力丧失。可以针对这些信号级联反应的药物干预措施,通过防止感觉细胞损伤,具有保留残余听力的巨大潜力。胆汁盐已在人体的各个部位显示出有效的抗氧化剂和消炎剂功效。然而,它们对内耳外伤的功效从未被探索过。这项研究的目的是确定胆汁盐衍生物牛磺脱氧胆酸(TDCA)是否可以预防感觉细胞损伤。体外电极插入创伤(EIT)的模型。从出生后第3天(P-3)大鼠解剖Corti(OC)外植体器官,并置于无血清培养基中。外植体分为对照组和实验组:(1)未经处理的对照组;(2)企业所得税;(3)EIT + TDCA(不同浓度)。测定了毛细胞(HC)的密度,凋亡通路(裂解的半胱天冬酶3)的分析,活性氧水平(ROS)以及诱导型一氧化氮合酶(iNOS)活性和线粒体膜电位(MMP)。TDCA治疗以剂量依赖性方式提供了针对HC丢失的显着耳保护。耳保护的分子机制涉及降低氧化应激,降低iNOS的水平以及废除裂解的半胱天冬酶3的产生。体外 并应探索开发药物干预措施,以保留耳蜗植入后残留的听力。

更新日期:2020-07-14
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