The effects of tempol, 3-aminobenzamide and nitric oxide synthase inhibitors on acoustic injury of the mouse cochlea
The effects of tempol, 3-aminobenzamide and nitric oxide synthase inhibitors on acoustic injury of the mouse cochlea
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DOI：
10.1016/j.heares.2005.12.008
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发表时间：
2006-04-01
期刊：
影响因子：
2.8
通讯作者：
Hara, Akira
中科院分区：
文献类型：
--
作者：
Murashita, Hidekazu;Tabuchi, Keiji;Hara, Akira
氧自由基参与耳蜗声损伤的发病机制。本研究旨在探讨超氧阴离子清除剂tempol、聚腺苷二磷酸核糖合成酶（PARS）抑制剂3-氨基苯甲酰胺、非选择性一氧化氮合酶（NOS）抑制剂N-硝基-（L）-精氨酸、选择性神经元NOS抑制剂7-硝基吲唑和选择性诱导型NOS抑制剂氨基胍对声损伤的影响。将小鼠暴露于110-128 dB SPL的4 kHz纯音4 h。Tempol、3-氨基苯甲酰胺或N-硝基-（L）-精氨酸在声过度刺激发作前立即腹腔内给药，而7-硝基吲唑或氨基胍在声过度刺激发作前立即开始每12小时腹腔内给药。在超声波刺激后1周和2周，观察听性脑干反应（ABR）阈值偏移和毛细胞丢失情况。Tempol和3-氨基苯甲酰胺显着保护耳蜗免受声损伤，而NOS抑制剂没有发挥任何保护作用。这些结果表明，活性氧和PARS参与了耳蜗的声损伤。然而，一氧化氮和一氧化氮合酶在声损伤中的作用还需进一步研究。(c)2006 Elsevier B. V.保留所有权利。
Oxygen free radicals have been implicated in the pathogenesis of acoustic injury of the cochlea. The purpose of this study was to evaluate the effects of tempol (a superoxide anion scavenger), 3-aminobenzamide (a poly (ADP-ribose) synthetase (PARS) inhibitor), N-nitro-(L)-arginine (a non-selective nitric oxide synthase (NOS) inhibitor), 7-nitroindazole (a selective neuronal NOS inhibitor) and aminoguanidine (a selective inducible NOS inhibitor) on acoustic injury. Mice were exposed to a 4 kHz pure tone of 110-128 dB SPL for 4 h. Tempol, 3-amino benzamide or N-nitro-(L)-arginine was intraperitoneally administered immediately before the onset of acoustic overexposure, while 7-nitroindazole or aminoguanidine was intraperitoneally administered every 12 h starting immediately before the onset of acoustic overexposure. The threshold shift of the auditory brainstem response (ABR) and hair cell loss were then evaluated one and two weeks after acoustic overexposure. Tempol and 3-aminobenzamide significantly protected the cochlea against acoustic injury, whereas the NOS inhibitors did not exert any protective effect. These findings suggest that reactive oxygen species and PARS are involved in acoustic injury of the cochlea. However, further study is necessary to elucidate the roles of nitric oxide and nitric oxide synthase in acoustic injury. (c) 2006 Elsevier B.V. All rights reserved.