Novel oral multifunctional antioxidant prevents noise-induced hearing loss and hair cell loss

Hear Res. 2020 Mar 15;388:107880. doi: 10.1016/j.heares.2019.107880. Epub 2020 Jan 3.

Abstract

Oxidative stress is a major contributor to noise-induced hearing loss, the most common cause of hearing loss among military personnel and young adults. HK-2 is a potent, orally-active, multifunctional, redox-modulating drug that has been shown to protect against a wide range of neurological disorders with no observed side effects. HK-2 protected cochlear HEI-OC1 cells against various forms of experimentally-induced oxidative stressors similar to those observed during and after intense noise exposure. The mechanisms by which HK-2 protects cells is twofold, first by its ability to reduce oxidative stress generated by free radicals, and second, by its ability to complex biologically active transition metals such as Fe+2, thus reducing their availability to participate in the Fenton reaction where highly toxic hydroxyl radicals are generated. For the rat in vivo studies, HK-2 provided significant protection against noise-induced hearing loss and hair cell loss. Noise-induced hearing loss was induced by an 8-16 kHz octave band noises presented for 8 h/d for 21 days at an intensity of 95 dB SPL. In the Prevention study, HK-2 was administered orally beginning 5 days before the start of the noise and ending 10 days after the noise. Treatment with HK-2 dose-dependently reduced the amount of noise-induced hearing impairment, reflected in the cochlear compound action potential, and noise-induced hair cell loss. In a subsequent Rescue experiment in which HK-2 was administered for 10 days starting after the noise was turned off, HK-2 also significantly reduced the amount of hearing impairment, but the effect size was substantially less than in the Prevention studies. HK-2 alone did not adversely affect HEI-OC1 cell viability, nor did it cause any adverse changes in rat body weight, behavior, cochlear function or hair cell integrity. Thus, HK-2 is a novel, safe, orally-deliverable and highly effective otoprotective compound with considerable potential for preventing hearing loss from noise and other hearing disorders linked to excessive oxidative stress.

Keywords: Hair cell loss; Hearing loss; Noise exposure; Otoprotection; Oxidative stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antioxidants / administration & dosage*
  • Cell Line
  • Disease Models, Animal
  • Hair Cells, Auditory / drug effects*
  • Hair Cells, Auditory / metabolism
  • Hearing / drug effects*
  • Hearing Loss, Noise-Induced / metabolism
  • Hearing Loss, Noise-Induced / physiopathology
  • Hearing Loss, Noise-Induced / prevention & control*
  • Oxidative Stress / drug effects*
  • Rats, Sprague-Dawley
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Reactive Nitrogen Species
  • Reactive Oxygen Species