N-Acetyl L-cysteine does not protect against premature age-related hearing loss in C57BL/6J mice:: A pilot study
N-Acetyl L-cysteine does not protect against premature age-related hearing loss in C57BL/6J mice:: A pilot study
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DOI：
10.1016/j.heares.2006.07.003
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发表时间：
2007-04-01
期刊：
影响因子：
2.8
通讯作者：
Alagramam, Kumar N.
中科院分区：
文献类型：
--
作者：
Davis, Rickie R.;Kuo, Ming-Wen;Alagramam, Kumar N.
一种能够预防年龄相关性听力损失的化合物在老龄化人口中将非常有用。N-乙酰-L-半胱氨酸(L-NaC)已被证明对噪声暴露具有保护作用，噪声暴露会导致氧化应激增加。在不受环境因素影响的情况下，有证据表明，老鼠的年龄相关性听力损失(AHL)与不止一个基因位点有关，进而与人类也是如此。我们的假设是AHL缺陷导致对氧化应激的敏感性增加，L-NAC将能够保护早熟AHL小鼠模型C57BL/6J(136)小鼠的听力。将L-NAC加入B6小鼠常规水瓶中(实验组)，随机给予。另一组饮用普通自来水。每月进行听力测试，以产生听性脑干反应(ABR)的能力。在最后的ABR测试后，过量服用阿维汀的小鼠被处死，取耳朵并量化毛细胞损失。在饮水中加入L-NAC的对照组与对照组的听性脑干反应阈值和组织病理学检查均无差异。与L-NAC对噪声性听力损失的保护作用相比，本研究中缺乏保护作用可能是由于(I)剂量水平；(Ii)治疗时间；(Iii)年龄导致听力损失的生化机制；或(Iv)小鼠代谢L-NAC的方式。(C)2006爱思唯尔B.V.保留所有权利。
A compound capable of preventing age-related hearing loss would be very useful in an aging population. N-acetyl-L-cysteine (L-NAC) has been shown to be protective against noise exposure, a condition that leads to increased oxidative stress. Not withstanding environmental factors, there is evidence that age-related hearing loss (AHL) in the mouse is linked to more than one genetic loci and, by extension, in humans. Our hypothesis is that AHL defect results in increased sensitivity to oxidative stress and L-NAC would be able to protect the hearing of a mouse model of pre-mature AHL, the C57BL/6J (136) mouse strain. L-NAC was added to the regular water bottle of B6 mice (experimental group) and available ad lib. The other group received normal tap water. Hearing was tested monthly by the ability to generate the auditory brainstem response (ABR). After the final ABR test, mice were sacrificed by an overdose of Avertin, ears were harvested and hair cell loss was quantified. There was no difference in ABR thresholds or in histopathology between the control group and the group receiving L-NAC in their drinking water. In contrast to the protective effects Of L-NAC against noise-induced hearing loss, the lack of protective effect in this study may be due to (i) the dosage level; (ii) the duration of treatment; (iii) the biochemical mechanisms underlying age-induced hearing loss; or (iv) how the mouse metabolizes L-NAC. (C) 2006 Elsevier B.V. All rights reserved.