Fechter Laurence D, Gearhart Caroline, Shirwany Najeeb A
Research Service Jerry Pettis Memorial Veterans Medical Center, Loma Linda, CA 92357, USA.
J Assoc Res Otolaryngol. 2004 Mar;5(1):90-8. doi: 10.1007/s10162-003-4028-8. Epub 2003 Dec 18.
Acrylonitrile, one of the 50 most commonly produced industrial chemicals, has recently been identified as a promoter of noise-induced hearing loss (NIHL). This agent has the potential to produce oxidative stress through multiple pathways. We hypothesize that acrylonitrile potentiates NIHL as a consequence of oxidative stress. The objectives of this study were to characterize acrylonitrile exposure conditions that promote permanent NIHL in rats and determine the ability of this nitrile to produce auditory dysfunction by itself. Additionally, we sought to determine whether a spin-trap agent that can form adducts with ROS would protect against the effects of acrylonitrile. Acrylonitrile administration produced significant elevation in NIHL detected as a loss in compound action potential sensitivity. The effect was particularly robust for high-frequency tones and particularly when acrylonitrile and noise were given on repeated occasions. Acrylonitrile by itself did not disrupt threshold sensitivity. Administration of the spin-trap agent phenyl- N- tert-butylnitrone (PBN), given to rats prior to acrylonitrile and noise, did block the elevation of NIHL by acrylonitrile. However, PBN at the dose and time interval given was ineffective in protecting auditory function in subjects exposed to noise alone. The results suggest that oxidative stress may play a role in the promotion of NIHL by acrylonitrile.
丙烯腈是最常生产的50种工业化学品之一,最近被确定为噪声性听力损失(NIHL)的促进剂。这种物质有可能通过多种途径产生氧化应激。我们假设丙烯腈由于氧化应激而增强NIHL。本研究的目的是确定促进大鼠永久性NIHL的丙烯腈暴露条件,并确定这种腈本身产生听觉功能障碍的能力。此外,我们试图确定一种能与活性氧形成加合物的自旋捕获剂是否能预防丙烯腈的影响。给予丙烯腈后,复合动作电位敏感性损失检测到的NIHL显著升高。这种效应在高频音调时尤为明显,特别是当反复给予丙烯腈和噪声时。丙烯腈本身不会破坏阈值敏感性。在给予丙烯腈和噪声之前给大鼠施用自旋捕获剂苯基-N-叔丁基硝酮(PBN),确实能阻止丙烯腈引起的NIHL升高。然而,在给定的剂量和时间间隔下,PBN对仅暴露于噪声的受试者的听觉功能保护无效。结果表明,氧化应激可能在丙烯腈促进NIHL中起作用。