Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Institute of Otolaryngology, Università Cattolica del Sacro Cuore, Rome, Italy; CNR Institute of Cell Biology and Neurobiology, Monterotondo, Italy.
Institute of Otolaryngology, Università Cattolica del Sacro Cuore, Rome, Italy; CNR Institute of Cell Biology and Neurobiology, Monterotondo, Italy.
Free Radic Biol Med. 2019 May 1;135:46-59. doi: 10.1016/j.freeradbiomed.2019.02.022. Epub 2019 Feb 22.
Hearing loss caused by exposure to recreational and occupational noise remains a worldwide disabling condition and dysregulation of redox homeostasis is the hallmark of cochlear damage induced by noise exposure. In this review we discuss the dual function of ROS to both promote cell damage (oxidative stress) and cell adaptive responses (ROS signaling) in the cochlea undergoing a stressful condition such as noise exposure. We focus on animal models of noise-induced hearing loss (NIHL) and on the function of exogenous antioxidants to maintaining a physiological role of ROS signaling by distinguishing the effect of exogenous "direct" antioxidants (i.e. CoQ, NAC), that react with ROS to decrease oxidative stress, from the exogenous "indirect" antioxidants (i.e. nutraceutics and phenolic compounds) that can activate cellular redox enzymes through the Keap1-Nrf2-ARE pathway. The anti-inflammatory properties of Nrf2 signaling are discussed in relation to the ROS/inflammation interplay in noise exposure. Unveiling the mechanisms of ROS regulating redox-associated signaling pathways is essential in providing relevant targets for innovative and effective therapeutic strategies against NIHL.
由于接触娱乐性和职业性噪声而导致的听力损失仍然是一种全球性的致残状况，而氧化还原平衡失调是噪声暴露引起耳蜗损伤的标志。在这篇综述中，我们讨论了 ROS 的双重功能，即在经历噪声暴露等应激条件时，ROS 既能促进细胞损伤（氧化应激），又能促进细胞适应性反应（ROS 信号转导）。我们重点介绍了噪声性听力损失（NIHL）的动物模型，以及外源性抗氧化剂在维持 ROS 信号转导生理作用方面的功能，区分了外源性“直接”抗氧化剂（即 CoQ、NAC）与外源性“间接”抗氧化剂（即营养保健品和酚类化合物）的作用，前者与 ROS 反应以减少氧化应激，后者可以通过 Keap1-Nrf2-ARE 通路激活细胞氧化还原酶。还讨论了 Nrf2 信号转导的抗炎特性与噪声暴露中 ROS/炎症相互作用的关系。揭示 ROS 调节与氧化还原相关的信号通路的机制对于提供针对 NIHL 的创新和有效的治疗策略的相关靶点至关重要。
