Ding Dalian, Zhang Jianghui, Liu Fang, Li Peng, Qi Weidong, Xing Yazhi, Shi Haibo, Jiang Haiyan, Sun Hong, Yin Shankai, Salvi Richard
Center for Hearing and Deafness, State University of New York at Buffalo, United States.
The Third People's Hospital of Chengdu, Chengdu, China.
J Otol. 2020 Mar;15(1):36-40. doi: 10.1016/j.joto.2019.11.005. Epub 2019 Dec 3.
The imbalance of reactive oxygen species and antioxidants is considered to be an important factor in the cellular injury of the inner ear. At present, great attention has been placed on oxidative stress. However, little is known about fighting oxidative stress. In the current study, we evaluated antioxidant-induced cochlear damage by applying several different additional antioxidants. To determine whether excessive antioxidants can cause damage to cochlear cells, we treated cochlear explants with 50 μM M40403, a superoxide dismutase mimetic, 50 μM coenzyme Q-10, a vitamin-like antioxidant, or 50 μM d-methionine, an essential amino acid and the important antioxidant glutathione for 48 h. Control cochlear explants without the antioxidant treatment maintained their normal structures after incubation in the standard serum-free medium for 48 h, indicating the maintenance of the inherent oxidative and antioxidant balance in these cochlear explants. In contrast, M40403 and coenzyme Q-10-treated cochlear explants displayed significant hair cell damage together with slight damage to the auditory nerve fibers. Moreover, d-methiodine-treated explants exhibited severe damage to the surface structure of hair cells and the complete loss of the spiral ganglion neurons and their peripheral fibers. These results indicate that excessive antioxidants are detrimental to cochlear cells, suggesting that inappropriate dosages of antioxidant treatments can interrupt the balance of the inherent oxidative and antioxidant capacity in the cell.
活性氧与抗氧化剂之间的失衡被认为是内耳细胞损伤的一个重要因素。目前，氧化应激已受到高度关注。然而，对抗氧化应激的了解却很少。在本研究中，我们通过应用几种不同的额外抗氧化剂来评估抗氧化剂诱导的耳蜗损伤。为了确定过量的抗氧化剂是否会对耳蜗细胞造成损伤，我们用50μM的超氧化物歧化酶模拟物M40403、50μM的维生素样抗氧化剂辅酶Q-10或50μM的必需氨基酸d-蛋氨酸（也是重要的抗氧化剂谷胱甘肽的前体）处理耳蜗外植体48小时。未经抗氧化剂处理的对照耳蜗外植体在标准无血清培养基中孵育48小时后保持其正常结构，这表明这些耳蜗外植体中固有氧化和抗氧化平衡得以维持。相比之下，用M40403和辅酶Q-10处理的耳蜗外植体显示出明显的毛细胞损伤以及对听神经纤维的轻微损伤。此外，用d-蛋氨酸处理的外植体表现出毛细胞表面结构的严重损伤以及螺旋神经节神经元及其外周纤维的完全丧失。这些结果表明，过量的抗氧化剂对耳蜗细胞有害，这表明不适当剂量的抗氧化剂治疗会破坏细胞内固有氧化和抗氧化能力的平衡。
