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

Autor: Chen GD; Center for Hearing and Deafness and Department of Communicative Disorders and Sciences, University at Buffalo, Buffalo, NY, 14214, USA., Daszynski DM; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Ding D; Center for Hearing and Deafness and Department of Communicative Disorders and Sciences, University at Buffalo, Buffalo, NY, 14214, USA., Jiang H; Center for Hearing and Deafness and Department of Communicative Disorders and Sciences, University at Buffalo, Buffalo, NY, 14214, USA., Woolman T; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA., Blessing K; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Therapeutic Vision, Inc., Elkhorn, NE, 68022, USA., Kador PF; Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE, 68198, USA; Therapeutic Vision, Inc., Elkhorn, NE, 68022, USA., Salvi R; Center for Hearing and Deafness and Department of Communicative Disorders and Sciences, University at Buffalo, Buffalo, NY, 14214, USA. Electronic address: salvi@buffalo.edu.
Jazyk: angličtina
Zdroj: Hearing research [Hear Res] 2020 Mar 15; Vol. 388, pp. 107880. Date of Electronic Publication: 2020 Jan 03.
DOI: 10.1016/j.heares.2019.107880
Abstrakt: 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.
Competing Interests: Declaration of competing interest Peter Kador is the President of Therapeutic Vision and hold the patent on HK-2. Dr. Salvi was the PI on a subaward on an NIH grant (1R43DC016766-01) to Therapeutic Vision to test the efficacy of HK-2.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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