Ebselen prevents noise-induced excitotoxicity and temporary threshold shift.
This investigation tested the hypothesis that a noise-induced temporary threshold shift (TTS) can be attenuated by a peroxynitrite scavenger, ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one). Guinea pigs received an oral dose of the vehicle or 10 mg/kg ebselen 1h before exposure to 115 dB SPL 4-kHz octave band noise for 3 h. In controls, auditory brainstem response (ABR) thresholds increased by 25-45 dB immediately after noise and returned to pre-exposure baseline thresholds 7 days later. Ebselen eliminated this ABR threshold shift following noise exposure. In controls, swelling of the afferent dendrites beneath the inner hair cells was evident immediately after noise, whereas ebselen significantly reduced this pathology. These findings suggest that scavenging peroxynitrite can attenuate noise-induced excitotoxicity and, thereby, TTS.
Yamasoba
Tatsuya
T
Department of Otolaryngology - Head and Neck Surgery, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. tyamasoba-tky@umin.ac.jp
Pourbakht
Akram
A
Sakamoto
Takashi
T
Suzuki
Mitsuya
M
D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects*; D001393:Azoles / Q000494:pharmacology* / Q000627:therapeutic use; D003056:Cochlear Nerve / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D016166:Free Radical Scavengers / Q000494:pharmacology / Q000627:therapeutic use; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism; D006319:Hearing Loss, Sensorineural / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D054833:Isoindoles; D008297:Male; D009410:Nerve Degeneration / Q000503:physiopathology / Q000517:prevention & control*; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009622:Noise / Q000009:adverse effects*; D016566:Organoselenium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D001393:Azoles; D018691:Excitatory Amino Acid Antagonists; D016166:Free Radical Scavengers; D005609:Free Radicals; D054833:Isoindoles; D018696:Neuroprotective Agents; D016566:Organoselenium Compounds; D018698:Glutamic Acid; C042986:ebselen