Noise-induced hearing loss in mice treated with antiretroviral drugs

Noise-induced hearing loss in mice treated with antiretroviral drugs
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DOI:
10.1016/j.heares.2008.01.016
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发表时间:
2008-05-01
期刊:
影响因子:
2.8
通讯作者:
Lonsbury-Martin, Brenda L.
Lonsbury-Martin, Brenda L.
中科院分区:
医学1区
文献类型:
--
作者:
Bektas, Devrim;Martin, Glen K.;Lonsbury-Martin, Brenda L.

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本文报告的 CBA/CaJ 小鼠结果描述了使用 2f(1)-f(2) 畸变产​​物耳声发射 (DPOAE) 和听觉脑干反应 (ABR) 的测量,定期服用常见抗逆转录病毒药物组合对外毛细胞 (OHC) 功能的影响。具体来说,实验小鼠在 3 个月的时间内每天接受溶解在饮用水中的核苷逆转录酶抑制剂 (NRTI)、齐多夫定 (ZDV) 和拉米夫定 (3TC) 的治疗,而对照小鼠则接受未经处理的水。 NRTI 治疗前后 12 周的 DPOAE 水平和 ABR 检测阈值在实验组和对照组之间没有差异。为了评估 NRTI 治疗是否会加剧噪声过度暴露对 OHC 功能的不利影响,实验小鼠和对照小鼠在 1 周后仍处于药物治疗期间,暴露于 105 dB SPL 的 10 kHz 倍频程噪声 (OBN) 下 1 小时。声音过度暴露事件的一个主要结果是,与未治疗的对照动物相比,在暴露后 2 周,NRTI 预处理的小鼠表现出明显更大的 OBN 诱导的 DPOAE 水平永久性降低。这些发现支持这样的观点,即某些 NRTls 和强声音之间存在协同关系,因为这种暴露前药物治疗比单独的噪声暴露产生更大的噪声诱导的 DPOAE 活性降低。这种药物/噪声相互作用与 NRTls 对细胞线粒体活性的已知有害作用一致。 (c) 2008 Elsevier B.V. 保留所有权利。
The results reported here for CBA/CaJ mice describe the effects of regular dosing with a common antiretroviral drug combination on outer hair cell (OHC) function using measures of 2f(1)-f(2) distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs). Specifically, experimental mice were treated daily over a 3-mo period with the nucleoside reverse transcriptase inhibitors (NRTIs), zidovudine (ZDV) and lamivudine (3TC), dissolved in their drinking water, while their control counterparts received untreated water. DPOAE levels and ABR detection thresholds prior to and after 12 wk of NRTI treatment did not differ between experimental and control groups. To assess whether NRTI treatment potentiates the adverse effects of noise over-exposure on OHC function, both experimental and control mice were exposed I wk later, while still on the drug regimen, to a 10-kHz octave-band noise (OBN) at 105-dB SPL for I h. A major outcome of the sound over-exposure episode was that the NRTI-pretreated mice showed significantly greater permanent OBN-induced reductions in DPOAE levels at 2 wk postexposure than were observed for the untreated control animals. These findings support the notion that a synergistic relationship exists between certain NRTls and intense sounds in that such pre-exposure drug treatments produced greater noise-induced decreases in DPOAE activity than did noise exposure alone. This drug/noise interaction is consistent with the known harmful effects of NRTls on cellular mitochondrial activity. (c) 2008 Elsevier B. V. All rights reserved.