Edaravone protects the vestibular periphery from free radical-induced toxicity in response to perilymphatic application of (+/-)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid.
Intracochlear infusion of (+/-)-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) was performed with a syringe pump in guinea pigs, and peripheral vestibular dysfunction was induced. Animals were administered edaravone systemically or topically. In the systemic application group, animals were administered edaravone once a day for 7 days after AMPA infusion. In the topical application group, edaravone-soaked gelfoam was placed on the round window membrane just after, 12 h after or 24 h after AMPA infusion. Spontaneous nystagmus was observed after AMPA infusion. Immunohistochemistry for 4-hydroxy-2-nonenal (4-HNE), a marker of free radical-induced lipid peroxidation, was performed 24 h after AMPA infusion. In addition, caloric tests were performed to evaluate vestibular function 1 week after AMPA infusion. Animals in both groups showed decreased spontaneous nystagmus, but results were not significant. Animals treated topically with edaravone within 12 h of AMPA infusion showed normal morphology of the ampullar sensory epithelia of the lateral semicircular canals and showed a good response to the caloric tests. 4-HNE immunoreactivity in the sensory epithelia was very low in these animals. In contrast, untreated animals and animals treated with edaravone systemically or topically 24 h after AMPA infusion showed morphologic hair cell damage, reduced caloric response and remarkable 4-HNE immunoreactivity in the sensory epithelia. These results indicate that topical application of edaravone within 12 h after damage protects the vestibular periphery from free radical-induced toxicity in response to intracochlear infusion of AMPA.
Shimogori
Hiroaki
H
Department of Otolaryngology, Yamaguchi University School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan. shimo-h@yamaguchi-u.ac.jp
Takemoto
Tsuyoshi
T
Mikuriya
Takefumi
T
Yamashita
Hiroshi
H
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000077553:Edaravone; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage / Q000633:toxicity; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D007260:Infusion Pumps; D008297:Male; D009759:Nystagmus, Pathologic / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control; D012027:Reflex, Vestibulo-Ocular / Q000187:drug effects; D015837:Vestibular Diseases / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D014724:Vestibular Function Tests; D014722:Vestibule, Labyrinth / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000008:administration & dosage / Q000633:toxicity*
D000447:Aldehydes; D018690:Excitatory Amino Acid Agonists; D016166:Free Radical Scavengers; D005609:Free Radicals; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C027576:4-hydroxy-2-nonenal; D000077553:Edaravone; D000983:Antipyrine