Institute of Otolaryngology, Università Cattolica School of Medicine, Rome, Italy; Institute of Cell Biology and Neurobiology, CNR, Monterotondo, Italy.
Institute of Otolaryngology, Università Cattolica School of Medicine, Rome, Italy.
Free Radic Biol Med. 2016 Dec;101:211-225. doi: 10.1016/j.freeradbiomed.2016.10.014. Epub 2016 Oct 18.
Experimental and human investigations have raised the level of concern about the potential ototoxicity of organic solvents and their interaction with noise. The main objective of this study was to characterize the effects of the combined noise and styrene exposure on hearing focusing on the mechanism of damage on the sensorineural cells and supporting cells of the organ of Corti and neurons of the ganglion of Corti. The impact of single and combined exposures on hearing was evaluated by auditory functional testing and histological analyses of cochlear specimens. The mechanism of damage was studied by analyzing superoxide anion and lipid peroxidation expression and by computational analyses of immunofluorescence data to evaluate and compare the oxidative stress pattern in outer hair cells versus the supporting epithelial cells of the organ of Corti. The oxidative stress hypothesis was further analyzed by evaluating the protective effect of a Coenzyme Q analogue, the water soluble Q, molecule known to have protective antioxidant properties against noise induced hearing loss and by the analysis of the expression of the endogenous defense enzymes. This study provides evidence of a reciprocal noise-styrene synergism based on a redox imbalance mechanism affecting, although with a different intensity of damage, the outer hair cell (OHC) sensory epithelium. Moreover, these two damaging agents address preferentially different cochlear targets: noise mainly the sensory epithelium, styrene the supporting epithelial cells. Namely, the increase pattern of lipid peroxidation in the organ of Corti matched the cell damage distribution, involving predominantly OHC layer in noise exposed cochleae and both OHC and Deiters' cell layers in the styrene or combined exposed cochleae. The antioxidant treatment reduced the lipid peroxidation increase, potentiated the endogenous antioxidant defense system at OHC level in both exposures but it failed to ameliorate the oxidative imbalance and cell death of Deiters' cells in the styrene and combined exposures. Current antioxidant therapeutic approaches to preventing sensory loss focus on hair cells alone. It remains to be seen whether targeting supporting cells, in addition to hair cells, might be an effective approach to protecting exposed subjects.
实验和人体研究提高了对有机溶剂潜在耳毒性及其与噪声相互作用的关注程度。本研究的主要目的是描述噪声与苯乙烯联合暴露对听力的影响，重点关注耳蜗感觉细胞和支持细胞以及柯蒂氏神经节神经元损伤的机制。通过听觉功能测试和耳蜗标本的组织学分析来评估单一和联合暴露对听力的影响。通过分析超氧阴离子和脂质过氧化表达以及对免疫荧光数据的计算分析来研究损伤机制，以评估和比较外毛细胞与柯蒂氏器支持上皮细胞的氧化应激模式。通过评估辅酶 Q 类似物水溶性 Q 分子对噪声性听力损失的保护作用以及对内源性防御酶表达的分析，进一步分析了氧化应激假说。本研究提供了基于氧化还原失衡机制的噪声-苯乙烯协同作用的证据，尽管损伤程度不同，但这种协同作用会影响外毛细胞（OHC）感觉上皮。此外，这两种损伤剂主要针对不同的耳蜗靶标：噪声主要作用于感觉上皮，苯乙烯主要作用于支持上皮细胞。即，柯蒂氏器的脂质过氧化增加模式与细胞损伤分布相匹配，在噪声暴露的耳蜗中主要涉及 OHC 层，而在苯乙烯或联合暴露的耳蜗中则涉及 OHC 和 Deiters' 细胞层。抗氧化治疗减少了脂质过氧化的增加，增强了两种暴露条件下 OHC 水平的内源性抗氧化防御系统，但未能改善苯乙烯和联合暴露中 Deiters' 细胞的氧化失衡和细胞死亡。目前预防感觉损失的抗氧化治疗方法主要针对毛细胞。此外，除了毛细胞之外，靶向支持细胞是否可能是保护暴露对象的有效方法，还有待观察。
