Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Horm Metab Res. 2013 Nov;45(12):887-92. doi: 10.1055/s-0033-1347200. Epub 2013 Jun 21.
Intense noise exposure and the application of ototoxic substances result in increased levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as nitric oxide (NO). In order to reduce the free NO concentration in the inner ear under pathological conditions, the use of natural cytoprotective substances such as 17β-estradiol is a promising therapeutic concept. In male guinea pigs the organ of Corti and the lateral wall were isolated from the cochlea and afterwards incubated for 6 h in cell-culture medium. 17β-Estradiol was adjusted in 2 concentrations to organ cultures of the right ears (12 animals per concentration). The left ears were used as controls. The NO production was quantified in the supernatant by chemiluminescence after incubation. Depending on the concentration, 17β-estradiol reduced NO in the organ of Corti by 43% (p=0.015) and 46% (p=0.026), respectively. In the lateral wall, the NO concentration was reduced by 24%, but without statistical significance (p=0.86). However, when analyzing the association between the 2 cochlear regions for each animal separately, the NO concentrations were lower in nearly all 17β-estradiol-treated ears compared to controls. In order to demonstrate the flexibility of the organ culture system, the NO donor DETA NONOate and the nitric oxide synthase inhibitors L-NAME and L-NMMA were applied. The electron microscopic analysis revealed a well-preserved cochlear cell morphology after incubation. The ability of 17β-estradiol to influence the NO production preferentially in the organ of Corti might offer new therapeutic perspectives for inner ear protection.
强烈的噪声暴露和耳毒性物质的应用会导致活性氧（ROS）和活性氮（RNS）水平升高，如一氧化氮（NO）。为了降低病理条件下内耳中游离 NO 浓度，使用 17β-雌二醇等天然细胞保护物质是一种有前途的治疗概念。在雄性豚鼠中，将耳蜗的柯蒂器和外侧壁从耳蜗中分离出来，然后在细胞培养液中孵育 6 小时。将 17β-雌二醇调整为右耳器官培养物的 2 个浓度（每个浓度 12 只动物）。左耳用作对照。孵育后通过化学发光法在上清液中定量 NO 生成。根据浓度的不同，17β-雌二醇分别使柯蒂器中的 NO 减少了 43%（p=0.015）和 46%（p=0.026）。在外侧壁中，NO 浓度降低了 24%，但无统计学意义（p=0.86）。然而，当分别分析每个动物的 2 个耳蜗区域之间的关联时，与对照相比，几乎所有用 17β-雌二醇处理的耳朵中的 NO 浓度都较低。为了证明器官培养系统的灵活性，应用了 NO 供体 DETA NONOate 以及一氧化氮合酶抑制剂 L-NAME 和 L-NMMA。电子显微镜分析显示孵育后耳蜗细胞形态保持良好。17β-雌二醇优先影响柯蒂器中 NO 产生的能力可能为内耳保护提供新的治疗前景。
