Free radical generation in the cochlea during combined exposure to noise and carbon monoxide: an electrophysiological and an EPR study

Free radical generation in the cochlea during combined exposure to noise and carbon monoxide: an electrophysiological and an EPR study
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DOI:
10.1016/s0378-5955(01)00366-5
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发表时间:
2001-11-01
期刊:
影响因子:
2.8
通讯作者:
Fechter, LD
Fechter, LD
中科院分区:
医学1区
文献类型:
--
作者:
Rao, DB;Moore, DR;Fechter, LD

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众所周知,噪声和一氧化碳(CO)联合暴露后的耳毒性比单独暴露在噪声中会导致更严重的永久性阈值漂移。我们以前已经证明,一氧化碳对噪声诱导的听力损伤的这种增强可以通过给药硝酮自旋捕捉剂来防止。虽然这种保护意味着通过自由基途径造成损伤,但药物诱导的保护并不能提供耳蜗中存在自由基的直接证据。这项研究的目的是证明同时暴露在噪声和CO下的耳蜗硝酮自旋加合物的实际存在。使用电生理终点。采用成年雄性Long Evans兜帽大鼠暴露于噪声和CO后,评价了硝酮自旋捕捉剂α-(4-吡啶-1-氧化物)-N-叔丁基硝酮(POBN)的防护作用。此外,通过电子顺磁共振波谱(EPR)对POBN自旋加合物进行了体外评价。噪声为倍频程频带噪声,中心频率为13.6 kHz,频率为100分贝(LIN),持续时间为2小时,CO使用量为1200ppm。电生理结果表明,POBN可以防止噪声和一氧化碳的联合暴露。EPR研究表明,暴露在噪声和一氧化碳环境中的动物耳蜗中存在POBN自旋加合物。因此,这项研究为噪声加CO暴露所致耳毒性是通过自由基介导的假说提供了证据。(C)2001 Elsevier Science B.V.保留所有权利。
Ototoxicity following combined exposure to noise and carbon monoxide (CO) is known to result in more severe permanent threshold shifts than exposure to noise alone. We have previously demonstrated that such potentiation of noise-induced auditory impairment by CO can be prevented by the administration of a nitrone spin-trapping agent. Although such protection implicates injury via free radical pathways, drug-induced protection does not provide direct evidence for the presence of free radicals in the cochlea. The objective of this study was to demonstrate the actual presence of nitrone spin adducts in the cochlea following simultaneous exposure to noise and CO. Using electrophysiological end-points. the protective effects of the nitrone spin-trapping agent alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) were assessed following combined exposure of adult male Long Evans hooded rats to noise and CO. In addition, an ex-vivo evaluation of POBN spin adducts was done by electron paramagnetic resonance spectroscopy (EPR). The noise used was octave band noise with center frequency 13.6 kHz at 100 dB(Lin) for a duration of 2 h. The level of CO used was 1200 ppm. Electro physiological results demonstrate that POBN protects against combined exposure to noise plus CO. The EPR study demonstrates POBN spin adducts in the cochleae of animals exposed to noise plus CO. Therefore, this study provides evidence to the hypothesis that ototoxicity due to noise plus CO exposure is mediated via free radicals. (C) 2001 Elsevier Science B.V. All rights reserved.