Lee Ji Eun, Nakagawa Takayuki, Kim Tae Soo, Endo Tsuyoshi, Shiga Atsushi, Iguchi Fukuichiro, Lee Sang Heun, Ito Juichi
Department of Otolaryngology--Head and Neck Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Acta Otolaryngol. 2004 Dec;124(10):1131-5. doi: 10.1080/00016480410017521.
It has been suggested that reactive radical species are involved in the mechanism of cisplatin-induced hearing loss. However, the nature of the free radicals involved is not fully understood. We examined the effects of two highly reactive species, hydroxyl radicals and peroxynitrite, on the auditory system of mice following cisplatin treatment.
Expression of 4-hydroxynonenal (HNE), a marker of lipid peroxidation by the hydroxyl radical, and nitrotyrosine (NT), a marker for protein peroxidation by peroxynitrite, was examined immunohistochemically in mouse cochleae injured by means of local application of cisplatin.
Loss of outer hair cells (OHCs) and spiral ganglia was found in cochleae affected by cisplatin. Both HNE and NT were detected in auditory epithelia and neurons damaged by cisplatin. Interestingly, auditory hair cells produced HNE, but not NT. Our findings indicate contributions by both HNE and NT to the degeneration of the auditory system due to cisplatin, and a crucial role of the hydroxyl radical in degeneration of OHCs.
The hydroxyl radical may be a critical target for a strategy aimed at protecting auditory function from cisplatin toxicity.
有研究表明，反应性自由基参与了顺铂所致听力损失的机制。然而，所涉及的自由基的性质尚未完全明确。我们研究了两种高反应性物质，即羟基自由基和过氧亚硝酸盐，对顺铂处理后小鼠听觉系统的影响。
通过局部应用顺铂损伤小鼠耳蜗，采用免疫组织化学方法检测4-羟基壬烯醛（HNE，羟基自由基引发脂质过氧化的标志物）和硝基酪氨酸（NT，过氧亚硝酸盐引发蛋白质过氧化的标志物）的表达。
在受顺铂影响的耳蜗中发现外毛细胞（OHC）和螺旋神经节缺失。在顺铂损伤的听觉上皮和神经元中均检测到HNE和NT。有趣的是，听觉毛细胞产生HNE，但不产生NT。我们的研究结果表明，HNE和NT均参与了顺铂所致听觉系统的退化，且羟基自由基在OHC退化中起关键作用。
羟基自由基可能是旨在保护听觉功能免受顺铂毒性影响的策略的关键靶点。
