Presbycusis has become a common sensory deficit in humans. Oxidative damage to mitochondrial DNA and mitochondrial dysfunction is strongly associated with the aging of the auditory system. A previous study established a mimetic rat model of aging using D-galactose (D-gal) and first reported that NADPH oxidase-dependent mitochondrial oxidative damage and apoptosis in the ventral cochlear nucleus (VCN) might contribute to D-gal-induced central presbycusis. In this study, we investigated the effects of apocynin, an NADPH oxidase inhibitor, on mitochondrial dysfunction and mitochondria-dependent apoptosis in the VCN of D-gal-induced aging model in rats. Our data showed that apocynin decreased NADPH oxidase activity, H2O2 levels, mitochondrial DNA common deletion, and 8-hydroxy-2-deoxyguanosine (8-OHdG) expression and increased total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) activity in the VCN of D-gal-induced aging model in rats. Moreover, apocynin also decreased the protein levels of phospho-p47phox (p-p47phox), tumor necrosis factor alpha (TNFα), and uncoupling protein 2 (UCP2) in the VCN of D-gal-induced aging model in rats. Meanwhile, apocynin alleviated mitochondrial ultrastructure damage and enhanced ATP production and mitochondrial membrane potential (MMP) levels in the VCN of D-gal-induced aging model in rats. Furthermore, apocynin inhibited cytochrome c (Cyt c) translocation from mitochondria to the cytoplasm and suppressed caspase 3-dependent apoptosis in the VCN of D-gal-induced aging model in rats. Consequently, our findings suggest that neuronal survival promoted by an NADPH oxidase inhibitor is a potentially effective method to enhance the resistance of neurons to central presbycusis.

中文翻译：

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NADPH氧化酶抑制剂Apocynin减轻D-半乳糖所致衰老模型大鼠腹侧耳蜗核的线粒体功能障碍和细胞凋亡。

老花眼已成为人类常见的感觉缺陷。线粒体DNA的氧化损伤和线粒体功能障碍与听觉系统的衰老密切相关。先前的研究使用D-半乳糖（D-gal）建立了模拟的衰老大鼠模型，并首先报道了NADPH氧化酶依赖性线粒体氧化损伤和腹侧耳蜗核（VCN）的凋亡可能有助于D-gal诱导的中枢性老年性耳聋。 。在这项研究中，我们调查了ADPcynin，一种NADPH氧化酶抑制剂，对D-gal诱导的衰老模型的VCN中线粒体功能障碍和线粒体依赖性细胞凋亡的影响。我们的数据表明，Apocynin降低了NADPH氧化酶活性，H2O2水平，线粒体DNA常见缺失，D-gal诱发衰老模型的VCN中的8和羟基-2-脱氧鸟苷（8-OHdG）表达以及总超氧化物歧化酶（T-SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性增加。此外，载脂蛋白A还降低了D-gal诱导的衰老模型的VCN中的磷酸化-p47phox（p-p47phox），肿瘤坏死因子α（TNFα）和解偶联蛋白2（UCP2）的蛋白水平。同时，Apocynin减轻了D-gal所致衰老模型的VCN中线粒体的超微结构损伤，并增强了ATP的产生和线粒体膜电位（MMP）的水平。此外，载脂蛋白抑制了大鼠D-gal衰老模型的VCN中细胞色素c（Cyt c）从线粒体到细胞质的转运，并抑制了caspase 3依赖性凋亡。所以，