Protective effect of edaravone against the ototoxicity of Pseudomonas aeruginosa exotoxin A.
CONCLUSIONS
Our findings suggest that edaravone can protect against cochlear damage caused by Pseudomonas aeruginosa exotoxin A (PaExoA).


OBJECTIVE
To analyze the protective effect of a free radical scavenger, edaravone, against the ototoxicity resulting from exposure of the middle ear to PaExoA.


METHODS
In nine groups of albino rats the following solutions were instilled either via the tympanic membrane into the round window niche [intratympanically (i.t.)] or intravenously (i.v.): edaravone (i.v.); edaravone (i.t.); PaExoA (i.t.) + edaravone (i.t.; simultaneously); PaExoA (i.t.) + edaravone (i.t.; 1 h after); PaExoA (i.t.) + edaravone (i.t.; 24 h after); PaExoA (i.t.) + edaravone (i.v.; simultaneously); PaExoA (i.t.) + edaravone (i.v.; 1 h after); PaExoA (i.t.) + edaravone (i.v.; 24 h after); PaExoA (i.t.) + saline (i.v.). Frequency-specific (2-20 kHz) auditory brainstem responses were measured to determine hearing thresholds before and 2, 5 and 10 days after instillation.


RESULTS
PaExoA had penetrated from the middle ear into the cochlea and caused hearing loss. This impairment was blocked by intratympanic injection of edaravone when given simultaneously or 1 h after the first instillation of PaExoA, or by intravenous injection of edaravone when given simultaneously. There were significant differences in protective effect between the intratympanic and intravenous routes.
Takumida
Masaya
M
Department of Otolaryngology, Faculty of Medicine, Hiroshima University, Minamiku, Hiroshima, Japan. masati@ipc.hiroshima-u.ac.jp
Anniko
Matti
M
D036002:ADP Ribose Transferases / Q000633:toxicity*; D000818:Animals; D000983:Antipyrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D001300:Audiometry, Evoked Response; D001309:Auditory Threshold / Q000187:drug effects*; D001427:Bacterial Toxins / Q000633:toxicity*; D004432:Ear, Middle / Q000187:drug effects; D000077553:Edaravone; D005098:Exotoxins / Q000633:toxicity*; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000627:therapeutic use*; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000517:prevention & control*; D007275:Injections, Intravenous; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014432:Tympanic Membrane / Q000187:drug effects; D037521:Virulence Factors / Q000633:toxicity*; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000983:Antipyrine; D001427:Bacterial Toxins; D000077553:Edaravone; D005098:Exotoxins; D016166:Free Radical Scavengers; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A