Acrylonitrile potentiates hearing loss and cochlear damage induced by moderate noise exposure in rats
Acrylonitrile potentiates hearing loss and cochlear damage induced by moderate noise exposure in rats
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DOI：
10.1016/j.taap.2004.08.015
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发表时间：
2005-04-01
影响因子：
3.8
通讯作者：
Fechter, LD
中科院分区：
文献类型：
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作者：
Pouyatos, B;Gearhart, CA;Fechter, LD
化学物质和药物的多样性可以加强噪声性听力损失(NIHL)，阻碍了预测这种相互作用的努力。我们假设，破坏内在抗氧化剂防御的化学污染物对增强NIHL具有重大风险。如果这是真的，那么丙烯腈(ACN)将有望增强NIHL。ACN是美国最常用的50种化学物质之一，它的代谢通过两条途径进行，这两条途径可能会扰乱内在活性氧物种(ROS)的缓冲系统：(1)它与谷胱甘肽结合，迅速消耗这种重要的抗氧化剂；(2)第二条途径涉及氰化物的形成，这可以抑制超氧化物歧化酶。我们假设，适度的噪音暴露本身不会导致永久性听力损失，可能会引发氧化应激，而ACN可能会通过扰乱固有的抗氧化防御机制使内耳对噪音更加敏感。用失真产物耳声发射(DPOAEs)和复合动作电位(CAP)波幅测定ACN单独(50 mg/kg，sc 5天)、单独噪声(95或97分贝倍频程噪声，4小时/天，连续5天)或ACN与噪声联合作用的暂时性和持续性效应。使用Corti器官的表面准备也研究了这些处理对毛细胞造成的组织病理学损害。单独来看，ACN和噪声暴露都不会导致任何永久性听力或毛细胞丧失；只有在噪声暴露的动物中测量到可逆的暂时性阈值漂移。然而，当ACN和噪声联合使用时，会导致永久性阈值移动(在7到40 kHz之间为13-16分贝)和DPOAE幅度的下降(在19 kHz时，高达25分贝)，以及显著的外毛细胞(OHC)损失(在13到47 kHz之间，第一排高达20%)。这项研究表明，ACN可以在符合人体暴露水平的噪声水平下增强NIHL，并且OHC是毒性的主要目标。虽然确切的机制尚不清楚，但结果与ROS在中等水平参与NIHL的假设是一致的。(C)2004 Elsevier Inc.保留所有权利。
The diversity of chemical and drugs that can potentiate noise-induced hearing loss (NIHL) has impeded efforts to predict such interactions. We have hypothesized that chemical contaminants that disrupt intrinsic antioxidant defenses hold significant risk for potentiating NIHL. If this is true, then acrylonitrile (ACN) would be expected to potentiate NIHL. ACN, one of the 50 most commonly used chemicals in the United States, is metabolized via two pathways that are likely to disrupt intrinsic reactive oxygen species (ROS) buffering systems: (1) it conjugates glutathione, depleting this important antioxidant rapidly; (2) a second pathway involves the formation of cyanide, which can inhibit superoxide dismutase. We hypothesized that moderate noise exposure, that does not produce permanent hearing loss by itself, could initiate oxidative stress and that ACN could render the inner ear more sensitive to noise by disrupting intrinsic antioxidant defenses. Temporary and persistent effects of ACN alone (50 mg/kg, sc 5 days), noise alone (95 or 97 dB octave band noise, 4 h/day for 5 days), or ACN in combination with noise were determined using distortion product otoacoustic emissions (DPOAEs) and compound action potential (CAP) amplitudes. Histopathological damage to hair cells resulting from these treatments was also investigated using surface preparations of the organ of Corti. Individually, neither ACN nor noise exposures caused any permanent hearing or hair cell loss; only a reversible temporary threshold shift was measured in noise-exposed animals. However, when given in combination, ACN and noise induced permanent threshold shifts (13-16 dB between 7 and 40 kHz) and a decrease in DPOAE amplitudes (up to 25 dB; at 19 kHz), as well as significant outer hair cell (OHC) loss (up to 20% in the first row between 13 and 47 kHz). This investigation demonstrates that ACN can potentiate NIHL at noise levels that are realistic in terms of human exposure, and that the OHCs are the main target of toxicity. While the exact mechanism is unknown, the results are consistent with the hypothesis of ROS involvement in NIHL at moderate levels. (c) 2004 Elsevier Inc. All rights reserved.