Gachon Research Institute of Pharmaceutical Sciences, College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, Korea.
R&D Center, Dongkook Pharm. Co., Ltd., Gyeonggi 16229, Korea.
Nutrients. 2020 Mar 29;12(4):947. doi: 10.3390/nu12040947.
Despite the excellent antimicrobial activity of aminoglycoside antibiotics, permanent inner ear damage associated with the use of these drugs has resulted in the need to develop strategies to address the ototoxic risk given their widespread use. In a previous study, we showed that avocado oil protects ear hair cells from damage caused by neomycin. However, the detailed mechanism by which this protection occurs is still unclear. Here, we investigated the auditory cell-protective mechanism of enhanced functional avocado oil extract (DKB122). RNA sequencing followed by pathway analysis revealed that DKB122 has the potential to enhance the expression of detoxification and antioxidant genes associated with glutathione metabolism (Hmox4, Gsta4, Mgst1, and Abcc3) in HEI-OC1 cells. Additionally, DKB122 effectively decreased ROS levels, resulting in the inhibition of apoptosis in HEI-OC1 cells. The expression of the inflammatory genes that encode chemokines and interleukins was also downregulated by DKB122 treatment. Consistent with these results, DKB122 significantly inhibited p65 nuclear migration induced by TNF-α or LPS in HEI-OC1 cells and THP-1 cells and the expression of inflammatory chemokine and interleukin genes induced by TNF-α was significantly reduced. Moreover, DKB122 treatment increased LC3-II and decreased p62 in HEI-OC1 cells, suggesting that DKB122 increases autophagic flux. These results suggest that DKB122 has otoprotective effects attributable to its antioxidant activity, induction of antioxidant gene expression, anti-inflammatory activity, and autophagy activation.
尽管氨基糖苷类抗生素具有优异的抗菌活性，但由于这些药物的广泛使用，永久性内耳损伤与它们的使用相关，这导致需要开发策略来解决耳毒性风险。在之前的研究中，我们表明鳄梨油可保护耳毛细胞免受新霉素引起的损伤。然而，这种保护作用发生的详细机制仍不清楚。在这里，我们研究了增强型功能性鳄梨油提取物（DKB122）对听觉细胞的保护机制。RNA 测序和途径分析表明，DKB122 具有增强与谷胱甘肽代谢相关的解毒和抗氧化基因（Hmox4、Gsta4、Mgst1 和 Abcc3）表达的潜力。此外，DKB122 还能有效降低 ROS 水平，从而抑制 HEI-OC1 细胞的凋亡。DKB122 处理还下调了编码趋化因子和白细胞介素的炎症基因的表达。与这些结果一致，DKB122 显著抑制了 TNF-α或 LPS 诱导的 HEI-OC1 细胞和 THP-1 细胞中 p65 核迁移，以及 TNF-α诱导的炎症趋化因子和白细胞介素基因的表达。此外，DKB122 处理增加了 HEI-OC1 细胞中的 LC3-II 并降低了 p62，表明 DKB122 增加了自噬通量。这些结果表明，DKB122 具有抗氧化活性、诱导抗氧化基因表达、抗炎活性和自噬激活等耳保护作用。
