TY - JOUR
T1 - Novel oral multifunctional antioxidant prevents noise-induced hearing loss and hair cell loss
AU - Chen, G. D.
AU - Daszynski, D. M.
AU - Ding, D.
AU - Jiang, H.
AU - Woolman, T.
AU - Blessing, K.
AU - Kador, P. F.
AU - Salvi, R.
N1 - Funding Information:
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.We sincerely thank Dr. Federico Kalinec, David Geffen School of Medicine, University of California, Los Angeles, CA for the gift of their HEI-OC1 cells. Supported by NIH 1R43DC016766-01 to Therapeutic Vision, Inc.
Funding Information:
We sincerely thank Dr. Federico Kalinec, David Geffen School of Medicine, University of California, Los Angeles, CA for the gift of their HEI-OC1 cells. Supported by NIH 1R43DC016766-01 to Therapeutic Vision, Inc. Appendix A
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/3/15
Y1 - 2020/3/15
N2 - 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.
AB - 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.
KW - Hair cell loss
KW - Hearing loss
KW - Noise exposure
KW - Otoprotection
KW - Oxidative stress
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U2 - 10.1016/j.heares.2019.107880
DO - 10.1016/j.heares.2019.107880
M3 - Article
C2 - 31945692
AN - SCOPUS:85077707350
SN - 0378-5955
VL - 388
JO - Hearing Research
JF - Hearing Research
M1 - 107880
ER -