Does erythropoietin augment noise induced hearing loss?
Does erythropoietin augment noise induced hearing loss?
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DOI：
10.1016/j.heares.2006.11.002
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发表时间：
2007-01-01
期刊：
影响因子：
2.8
通讯作者：
Thomsen, Jens
中科院分区：
文献类型：
--
作者：
Frederiksen, Birgitte Lidegaard;Caye-Thomasen, Per;Thomsen, Jens
噪声性听力损失可能是由于谷氨酸、氮氧化物和活性氧的过度释放引起的。这些因素对内耳的影响可能被促红细胞生成素（EPO）潜在地阻止或减少，正如先前证明的EPO对中枢神经系统和视网膜损伤的神经保护作用所表明的那样。本文报道了三个独立的试验，研究了红细胞生成素可以预防或减少噪声性听力损失的假设。试验采用三种不同给药方式、不同给药时间窗和不同鼠种。试验1：将豚鼠置于110 dB声压级、4-20 kHz宽带噪声（WBN）下8 h。噪声暴露24 h后，将EPO泵入圆窗膜，持续1周或单次中耳滴注。实验2，大鼠在105 dB声压、4-20 kHz WBN环境下暴露8 h。EPO在噪声暴露后1 h或14 h通过中耳单剂量滴注给药。实验3，将大鼠置于105 dB声压、4-20 kHz WBN环境8或3 × 8 h，在噪声暴露前1 h腹腔注射EPO。在所有试验中记录噪声暴露前后的耳声发射和听性脑干反应（16 kHz）。暴露在噪音中导致所有动物的听力丧失。在试验1中，任何治疗组均未出现听力恢复和改善。在试验2和试验3中，听力部分恢复。然而，在试验2中，EPO治疗动物的听力损失明显比对照组更严重。在试验3中，EPO处理动物暴露3 × 8小时的听力明显差于对照组。因此，令人惊讶的是，目前3项试验中的2项结果表明，促红细胞生成素实际上可能增加噪声性听力损失。这与绝大多数关于应激神经组织的研究报告中EPO的有益作用是矛盾的。在噪声暴露期间或之后，EPO可能通过潜在的血管收缩诱导改变耳蜗血管床的血流动力学。这可能是令人惊讶的发现的原因。(c) 2006 Elsevier B.V.版权所有
Noise-induced hearing loss may result from excessive release of glutamate, nitrogen oxide and reactive oxygen species. The effects of these factors on the inner ear may potentially be prevented or reduced by erythropoietin (EPO), as indicated by previously demonstrated neuro-protective effects of EPO upon damage to the central nervous system and the retina. This paper reports three separate trials, conducted to investigate the hypothesis that noise-induced hearing loss is prevented or reduced by erythropoietin. The trials employed three different modes of drug application, different administration time windows and different rodent species.In trial 1, guinea pigs were exposed to 110 dB SPL, 4-20 kHz wide band noise (WBN) for 8 h. EPO was administered to the round window membrane 24 h after noise exposure, either sustained by pump for a week or by single dose middle ear instillation. In trial 2, rats were exposed to 105 dB SPL, 4-20 kHz WBN for 8 h. EPO was administered by single dose middle ear instillation I or 14 h after noise exposure. In trial 3, rats were exposed to 105 dB SPL, 4-20 kHz WBN for 8 or 3 x 8 h. EPO was injected intraperitoneally I h before noise exposure. Oto-acoustic emissions and auditory brainstem responses (at 16 kHz) were recorded before and after noise exposure in all trials. The noise exposure induced a hearing loss in all animals. In trial 1, no recovery and no improvement of hearing occurred in any treatment group. In trial 2 and 3, a partial hearing recovery was seen. However, the hearing loss of the EPO treated animals was significantly worse than controls in trial 2. In trial 3, the hearing of the EPO treated animals exposed for 3 x 8 h was significantly worse than controls. Thus, surprisingly, the results from 2 of the 3 present trials indicate that erythropoietin may in fact augment noise-induced hearing loss. This is contradictory to the beneficial effect of EPO reported by the vast majority of studies on stressed neural tissues. EPO administration may alter the blood flow dynamics of the cochlear vascular bed during or after noise exposure, by a potential induction of vasoconstriction. This may be the cause of the surprising findings. (c) 2006 Elsevier B.V. All rights reserved.