EFFECT OF LEUKOTRIENE INHIBITOR ON OTOACOUSTIC EMISSIONS IN SALICYLATE OTOTOXICITY

Our previous work showed that salicylate ototoxicity is associated wit h decreased levels of prostaglandins (PGs) and increased levels of leu kotrienes (LTs) in the perilymph. Pretreatment with LT inhibitor was f ound to prevent salicylate ototoxicity. Other studies demonstrated tha t salicylate ototoxicity is associated with decreased cochlear blood f low, reversible changes in cochlear outer hair cells, and decreased ot oacoustic emissions. The purpose of our study was to determine the eff ect of LT blocker (Sch 37224) on transient-evoked otoacoustic emission s (TEOAEs) in salicylate or LT ototoxicity. Chinchillas were divided i nto five groups. Transient-evoked otoacoustic emissions were measured after salicylate application on the round window membrane (RWM), with (Group 1) and without (Group 2) LT blockade; after LTC4 (a type of leu kotriene) application on the RWM, with (Group 3) and without (Group 3) LT blockade; and in the control group after saline application on the RWM. The overall response differences from the baseline measurements over time in each case were compared with each other. Both salicylate and LTC4 application on the RWM were followed by significant decreases in TEOAEs, and the decrease was prevented by pretreatment with LT blo cker. There was no significant change in TEOAEs in the control group. Salicylate ototoxicity appears to be mediated by the elevated levels o f leukotrienes as a consequence of cyclooxygenase inhibition. This stu dy also provides further evidence that the site of action in salicylat e ototoxicity is the outer hair cell.