Ebselen attenuates cochlear damage caused by acoustic trauma.
Ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one), a seleno-organic compound, mimics glutathione peroxidase and reacts with peroxynitrite. It is reported to protect against gentamicin- and cisplatin-induced ototoxicity. We investigated whether it protects the cochlea from acoustic trauma. Male pigmented guinea pigs (250-300 g) with normal auditory brainstem response (ABR) thresholds were exposed for 5 h to 125 dB sound pressure level octave band noise centered at 4 kHz. One hour before and 18 h after exposure, they received orally 0.25 ml chloroform solution containing 0, 10, or 30 mg/kg ebselen (n=6, 5 and 5, respectively). The protective effect of ebselen was evaluated by ABR measurement and quantitative hair cell assessment. Treatment significantly (P<0.01) reduced the extent of permanent threshold shifts and outer hair cell loss. Interestingly, the protective effect of a 30 mg/kg dose was less than that of a 10 mg/kg dose. There were no adverse systemic or auditory function effects in three unexposed control subjects given 30 mg/kg ebselen. These findings indicate that ebselen attenuates noise-induced cochlear damage. The concentration that provides optimal protection against such damage has now to be determined.
Pourbakht
Akram
A
Department of Otolaryngology, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, 113-8655 Tokyo, Japan.
Yamasoba
Tatsuya
T
D000818:Animals; D001393:Azoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D003051:Cochlea / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D019610:Cytoprotection; D004056:Differential Threshold / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016057:Evoked Potentials, Auditory, Brain Stem; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000187:drug effects; D006317:Hearing Loss, Noise-Induced / Q000473:pathology* / Q000503:physiopathology*; D054833:Isoindoles; D008297:Male; D016566:Organoselenium Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*
D001393:Azoles; D054833:Isoindoles; D016566:Organoselenium Compounds; C042986:ebselen