Role of reactive radicals in degeneration of the auditory system of mice following cisplatin treatment
Role of reactive radicals in degeneration of the auditory system of mice following cisplatin treatment
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DOI：
10.1080/00016480410017521
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发表时间：
2004-12-01
影响因子：
1.4
通讯作者：
Ito, J
中科院分区：
文献类型：
--
作者：
Lee, JE;Nakagawa, T;Ito, J
目的：已有研究表明，活性自由基参与了顺铂致聋的机制。然而，所涉及的自由基的性质还不完全清楚。研究了羟基自由基和过氧亚硝酸根这两种高活性物质对顺铂作用后小鼠听觉系统的影响。材料与方法：用免疫组织化学方法检测了顺铂损伤小鼠耳蜗组织中羟基自由基脂质过氧化标志物4-羟基壬烯醛(HNE)和过氧亚硝酸根蛋白质过氧化标志物硝基酪氨酸(NT)的表达。顺铂损伤的听觉上皮细胞和神经元中均有HNE和NT的表达。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都参与了顺铂引起的听觉系统退化，而羟基自由基在毛细胞退化中起着关键作用。结论：羟基自由基可能是保护听功能免受顺铂毒性影响的策略的关键靶点。
Objective - 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.Material and Methods - 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.Results - 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.Conclusion - The hydroxyl radical may be a critical target for a strategy aimed at protecting auditory function from cisplatin toxicity.