Bas Esperanza, Martinez-Soriano Francisco, Láinez José M, Marco Jaime
Hospital Clinico Universitario Research Foundation, Valencia, Spain.
Acta Otolaryngol. 2009 Apr;129(4):385-9. doi: 10.1080/00016480802566279.
The calcineurin inhibitor tacrolimus (TCR) and the pineal gland hormone and antioxidant melatonin (MLT) have been shown to possess otoprotective properties against noise-induced hearing loss (NIHL). In contrast, dexamethasone (DXM) was not effective as an otoprotective agent against NIHL. Further studies are needed to understand the exact molecular mechanisms involved.
Exposure to noise pollution and use of audio devices for long periods of time at high volume is known to cause hearing loss or NIHL. Our goal was to evaluate the effectiveness of various known compounds such as the anti-inflammatory DXM, the antioxidant MLT and the immunosuppressant TCR against NIHL.
Thirty-two Wistar rats were randomly divided into groups that were then exposed to intense white noise at 120 dB SPL for 4 h. The day before and for a period of 14 days, test groups were administered one of the three compounds. The efficacy of the compounds against NIHL was determined after examining the shifts in the levels of distortion product otoacoustic emissions (DPOAEs) and changes in the threshold of auditory brainstem responses (ABRs). Cytocochleograms and determination of gene expression in whole rat cochlea were carried out at day 21.
Treatment with DXM had no otoprotective effect, while animals treated with MLT experienced an improvement in their hearing functionality. This effect, which is probably linked to MLT's ability to reduce c-fos and TNF-alpha gene expression thereby preventing outer hair cell (OHC) loss, was even more pronounced in week 3. For its part, TCR provided protection against injury to the cochlea from week 1, eventually leading to a full recovery in hearing. The compound reduced both c-fos and TNF-alpha expression, as well as OHC loss.
已证明钙调神经磷酸酶抑制剂他克莫司(TCR)以及松果体激素和抗氧化剂褪黑素(MLT)具有针对噪声性听力损失(NIHL)的耳保护特性。相比之下,地塞米松(DXM)作为针对NIHL的耳保护剂无效。需要进一步研究以了解其中的确切分子机制。
已知长时间暴露于噪声污染以及使用高音量音频设备会导致听力损失或NIHL。我们的目标是评估各种已知化合物,如抗炎药DXM、抗氧化剂MLT和免疫抑制剂TCR对NIHL的有效性。
将32只Wistar大鼠随机分组,然后使其暴露于120 dB SPL的高强度白噪声中4小时。在暴露前一天及为期14天的时间里,给测试组施用三种化合物之一。在检查畸变产物耳声发射(DPOAE)水平的变化以及听觉脑干反应(ABR)阈值的变化后,确定这些化合物对NIHL的疗效。在第21天进行细胞耳蜗图分析并测定全大鼠耳蜗中的基因表达。
DXM治疗没有耳保护作用,而用MLT治疗的动物听力功能有所改善。这种作用可能与MLT降低c-fos和TNF-α基因表达从而防止外毛细胞(OHC)损失的能力有关,在第3周时这种作用甚至更明显。就TCR而言,从第1周开始就为耳蜗提供了免受损伤的保护,最终导致听力完全恢复。该化合物降低了c-fos和TNF-α的表达以及OHC的损失。