Park J-S, Jou I, Park S M
1] Department of Pharmacology, Ajou University School of Medicine, Suwon, Korea [2] Department of Otolaryngology, Ajou University School of Medicine, Suwon, Korea [3] Neuroscience Graduate Program, Department of Biological Sciences, Ajou University School of Medicine, Suwon, Korea [4] Chronic inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-380, Korea.
1] Department of Pharmacology, Ajou University School of Medicine, Suwon, Korea [2] Neuroscience Graduate Program, Department of Biological Sciences, Ajou University School of Medicine, Suwon, Korea [3] Chronic inflammatory Disease Research Center, Ajou University School of Medicine, Suwon 443-380, Korea.
Cell Death Dis. 2014 Apr 24;5(4):e1200. doi: 10.1038/cddis.2014.170.
The overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) has been known to contribute to the pathogenesis of noise-induced hearing loss. In this study, we discovered that in BALB/c mice pretreatment with methylene blue (MB) for 4 consecutive days significantly protected against cochlear injury by intense broad-band noise for 3 h. It decreased both compound threshold shift and permanent threshold shift and, further, reduced outer hair cell death in the cochlea. MB also reduced ROS and RNS formation after noise exposure. Furthermore, it protected against rotenone- and antimycin A-induced cell death and also reversed ATP generation in the in vitro UB-OC1 cell system. Likewise, MB effectively attenuated the noise-induced impairment of complex IV activity in the cochlea. In addition, it increased the neurotrophin-3 (NT-3) level, which could affect the synaptic connections between hair cells and spiral ganglion neurons in the noise-exposed cochlea, and also promoted the conservation of both efferent and afferent nerve terminals on the outer and inner hair cells. These findings suggest that the amelioration of impaired mitochondrial electron transport and the potentiation of NT-3 expression by treatment with MB have a significant therapeutic value in preventing ROS-mediated sensorineural hearing loss.
已知活性氧(ROS)和活性氮(RNS)的过度产生会导致噪声性听力损失的发病机制。在本研究中,我们发现,在BALB/c小鼠中,连续4天用亚甲蓝(MB)预处理可显著保护其免受3小时强烈宽带噪声引起的耳蜗损伤。它降低了复合阈移和永久性阈移,进一步减少了耳蜗中外毛细胞的死亡。MB还减少了噪声暴露后ROS和RNS的形成。此外,它保护细胞免受鱼藤酮和抗霉素A诱导的细胞死亡,并在体外UB-OC1细胞系统中逆转ATP生成。同样,MB有效减轻了噪声引起的耳蜗中复合物IV活性的损伤。此外,它提高了神经营养因子-3(NT-3)的水平,这可能会影响噪声暴露耳蜗中毛细胞与螺旋神经节神经元之间的突触连接,还促进了外毛细胞和内毛细胞上的传出和传入神经末梢的保留。这些发现表明,用MB治疗改善线粒体电子传递受损和增强NT-3表达在预防ROS介导的感音神经性听力损失方面具有显著的治疗价值。