Creatine and tempol attenuate noise-induced hearing loss.
To define the role of free radical formation and potential energy depletion in noise induced hearing loss (NIHL), we measured the effectiveness of tempol (free radical scavenger) and creatine (enhances cellular energy storage) alone and in combination to attenuate NIHL. Guinea pigs were divided into four treatment groups: controls, 3% creatine diet (2 weeks prior to noise exposure), tempol (3 mM in drinking water 2 weeks prior to exposure), and creatine plus tempol and exposed to 120 dB SPL one-octave band noise centered at 4 kHz for 5 h. The noise-only control group showed frequency-dependent auditory threshold shifts (measured by auditory brainstem response, ABR) of up to 73 dB (16 kHz) on day 1, and up to 50 dB (8 kHz) on day 10. Creatine-treated subjects had significantly smaller ABR threshold shifts on day 1 and on day 10. Tempol alone significantly reduced ABR threshold shifts on day 10 but not on day 1. ABR shifts after combination treatment were similar to those in the creatine group. Hair cell loss on day 10 was equally attenuated by creatine and tempol alone or in combination. Our results indicate that the maintenance of ATP levels is important in attenuating both temporary and permanent NIHL, while the scavenging of free radicals provides protection from permanent NIHL.
Minami
Shujiro B
SB
Kresge Hearing Research Institute, University of Michigan, 1301 E. Ann Street, Ann Arbor, MI 48109-0506, USA.
Yamashita
Daisuke
D
Ogawa
Kaoru
K
Schacht
Jochen
J
Miller
Josef M
JM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D001309:Auditory Threshold / Q000187:drug effects / Q000502:physiology; D003051:Cochlea / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D003401:Creatine / Q000494:pharmacology* / Q000627:therapeutic use; D003497:Cyclic N-Oxides / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D009622:Noise / Q000009:adverse effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D013113:Spin Labels; D016896:Treatment Outcome
D000975:Antioxidants; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D005609:Free Radicals; D013113:Spin Labels; D000255:Adenosine Triphosphate; D003401:Creatine; C001803:tempol