PRACTICA OTO-RHINO-LARYNGOLOGICA
Vol. 99 No. 12 December 2006
Mechanism of Cochlear Protection and
Therapy for Inner Ear Diseases
Hiroshi Yamashita and Kazuma Sugahara
(Graduate School of Medicine, Yamaguchi University)
It is believed that the sensory cells are very fragile and that their function is difficult to recover after damage to the inner ear. Therefore, methods used for the protection of inner ear tissue against stress are important. We have studied the mechanism of hair cell protection. The review inculdes our recent studies on hair cell protection with clinical reagents. The effect of the free radical scavenger edaravone on acoustic trauma was investigated. Our results showed that edaravone could protect cochlear function against intense noise. The protective effects of the reagents tested were observed in the inner ear 9-21 hours after noise exposure. These results were supported by immunohistochemical analysis of 4-hydroxy-2-nonenal. An inducer of heat shock protein, teprenone, was used for cochlear protection. Western blot analysis showed that the expressions of Hsp70, 40, and 27 were increased 24-48 hours after the administration of a single dose of teprenone. In addition, daily administration of teprenone for 7 days could enhance Hsps expression more strongly than single dose administration. In test animals given teprenone before intense sound exposure, their ABR threshold elevations were lowered significantly. In addition, significantly fewer defects were observed in outer hair cells of the organ of Corti in animals treated with teprenone than in those of non-teprenone-treated animals.
These clinical reagents are candidates for cochlear protection therapy.
Key words :reactive oxygen species, heat shock protein, cochlear protection, noise trauma