Avenanthramide-C prevents noise- and drug-induced hearing loss while protecting auditory hair cells from oxidative stress

Abstract

Noise exposure or ototoxic drugs instigate various types of damage to the cochlea, resulting in hearing loss (HL). While the incidence of HL is growing continuously, there are, so far, no adequate drugs to prevent or treat HL. Avenanthramide (AVN), a natural product extracted from oats, has been reported to possess anti-oxidant/inflammatory properties, and protect several types of cells. In this study, we investigated whether AVN-C can protect auditory hair cells, and preserve hearing from noise trauma and ototoxic drugs. Wild-type C57BL/6 mice were used to generate several HL models. Serum and perilymphatic fluid samples were analyzed using mass spectrophotometry to detect AVN-C. AVN-C crossed the blood-labyrinth barrier, and was detected in the perilymph after systemic injection. Pretreatment by AVN-C 24 h before exposure to temporary threshold shift noise contributed to the preserving hearing. Moreover, in the case of permanent threshold shift, AVN-C provided significant protection from noise. AVN-C also strongly protected against deterioration in hearing due to kanamycin and furosemide (K + F). According to the results of our scanning electron microscopy analysis, many outer hair cells (OHCs) were destroyed by noise trauma, while AVN-C prevented these losses. OHC loss due to K + F was even more severe, even affecting the apex. Strikingly, AVN-C treatment maintained OHCs at a level comparable to normal cochlea. AVN-C reduced the dichlorofluorescin (DCF)-positive population in gentamicin-treated HEI-OC1 in vitro. The expressions of TNF-a, BAK, IL-1b, and Bcl-2 were attenuated by AVN-C, revealing its antioxidant effects. The results of this study show that AVN-C crosses the blood-labyrinth barrier and provide a significant protection against noise- and drug-induced ototoxicity. Hence, AVN-C is a good candidate for future therapy aimed at protecting against sensorineural HL.

Outcomes of Peptide Vaccine GV1001 Treatment in a Murine Model of Acute Noise-Induced Hearing Loss

“…Taking into consideration previous studies regarding the therapeutic effects of GV1001, we hypothesized that GV1001 might also exert otoprotective effects against NIHL, because excessive ROS/RNS generation and its signaling cascades, involving inflammatory and cell stress or apoptosis pathways are thought to underlie the causative mechanisms of NIHL. In support of this hypothesis, Avenanthramide-C that possesses antioxidant and anti-inflammatory properties was shown to exhibit a similar protective effect against noise-and drug-induced ototoxicity in the mouse model [15]. To the best of our knowledge, there have been no studies regarding the therapeutic effects of peptide vaccine GV1001 on NIHL.…”

“…GV1001 is also neuroprotective against beta-amyloid oligomers in neural stem cells, attributable to induction of cellular proliferation, anti-apoptotic and antioxidant effects, and mitochondrial stabilization [23]. Hence, this novel peptide vaccine may have additional potential applications in other medical conditions such as sudden sensorineural hearing loss or Meniere disease on the basis of the multipotent actions on the reduction of ROS/RNS, pro-inflammatory mediators and blocking proapoptotic caspases Interestingly, a recent study proposed that noise might loosen the blood-labyrinth-barrier; the highest perilymph concentration of the antioxidant AVN-C was noted 1 h after noise exposure [15]. In another study utilizing a guinea pig model, noise-induced ultrastructural changes in the blood-labyrinth barrier and decreased the immunoreactivities of tight junction proteins, suggesting that noise might affect blood-labyrinth barrier permeability [24].…”

Synergistic Effect of Methyl Jasmonate and Abscisic Acid Co-Treatment on Avenanthramide Production in Germinating Oats

“…Several studies show that Avn C exerts greater antioxidant activity than Avn A and B [ 16 , 17 , 18 , 38 , 39 ]. Dhakal et al [ 38 ] reported that Avn C from germinated oats exhibits anti-allergic and anti-inflammatory effects in mast cells, and Umugire et al [ 39 ] showed that Avn C exerts a strong protective effect on hearing loss caused by noise trauma. These results suggest Avn C as a promising candidate as a therapeutic for treating allergic diseases and hearing damage, given that Avn C can be provided through dietary products derived from oats.…”

Noise-Induced Hearing Loss: Updates on Molecular Targets and Potential Interventions

“…Notably, AVN-C has great water solubility and blood-labyrinth barrier permeability, suggesting pharmaceutical potential for NIHL treatment. Researchers have found that peritoneal injection of AVN-C protects hair cells from noise trauma by increasing antioxidant defense and decreasing proinflammatory cytokines like IL-1 β and Tnf [ 200 ].…”