Wang Weilong, Li Dan, Ding Xuerui, Zhao Qianqian, Chen Jiawei, Tian Keyong, Qiu Yang, Lu Lianjun
Department of Otolaryngology Head & Neck Surgery, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, China.
Department of Otorhinolaryngology, Hu County People's Hospital, Xi'an 710300, China.
Toxicol Lett. 2017 Sep 5;279:77-86. doi: 10.1016/j.toxlet.2017.07.903. Epub 2017 Aug 1.
Manganese (Mn) is an indispensable cofactor for many enzymes and a basic factor for many reproductive and metabolic pathways. However, exposure to high concentrations of Mn can result in deleterious effects on the central nervous system and peripheral nerves, including nerves associated with the auditory system. Based on our studies of cochlear organotypic cultures, Mn exposure induces a significant loss of hair cells (HCs), auditory nerve fibers (ANFs) and spiral ganglion neurons (SGNs) in a concentration-dependent manner. Additionally, N-acetylcysteine (NAC), a glutathione (GSH) provider and a direct scavenger of reactive oxygen species (ROS), clearly decreases Mn-induced ROS accumulation, caspase-3 activation and TUNEL staining, which indicate increased cell survival. Based on these results, Mn exposure exerts ototoxic and neurotoxic effects on the auditory system. Furthermore, 20mM NAC may prevent 1mM Mn-induced hair cell loss and axonal degeneration, indicating that NAC could be a promising drug for clinical applications.
锰（Mn）是许多酶不可或缺的辅助因子，也是许多生殖和代谢途径的基本要素。然而，接触高浓度的锰会对中枢神经系统和周围神经产生有害影响，包括与听觉系统相关的神经。基于我们对耳蜗器官型培养物的研究，锰暴露会以浓度依赖的方式导致毛细胞（HCs）、听神经纤维（ANFs）和螺旋神经节神经元（SGNs）显著损失。此外，N-乙酰半胱氨酸（NAC）是一种谷胱甘肽（GSH）提供者和活性氧（ROS）的直接清除剂，它能明显减少锰诱导的ROS积累、半胱天冬酶-3激活和TUNEL染色，这些表明细胞存活率增加。基于这些结果，锰暴露对听觉系统产生耳毒性和神经毒性作用。此外，20mM的NAC可能预防1mM锰诱导的毛细胞损失和轴突变性，这表明NAC可能是一种有前景的临床应用药物。
