Abstract
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.
Highlights
466 million people around the world experience hearing loss, including 34 million children [1]
Cell survival rate was measured after treatment with DKB122 in a cell-based model whereby House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were treated with neomycin to induce toxicity
Cells treated with neomycin (10 mM) for 24 h showed a decrease in viability of approximately 24.8%
Summary
466 million people around the world experience hearing loss, including 34 million children [1]. Aside from congenital causes, the etiologies of hearing loss include ear infections, noise, Nutrients 2020, 12, 947; doi:10.3390/nu12040947 www.mdpi.com/journal/nutrients. Nutrients 2020, 12, 947 aging, and ototoxic chemicals. It is believed that excessive noise and ototoxic chemicals result in inflammation of the inner ear, and drug ototoxicity, in particular, is one of the most preventable contributors to hearing loss. Aminoglycosides (AGs) are a well-known class of antibiotics for use against infections caused by gram-negative bacteria. AGs are both nephrotoxic [2] and ototoxic [3]. Despite their deleterious effects on the nephron and inner ear, AGs remain the most widely used antibiotics. Among AGs, neomycin is characterized as the most toxic, in the cochlea [4]
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