Effect of leukotriene inhibitor on otoacoustic emissions in salicylate ototoxicity.
Our previous work showed that salicylate ototoxicity is associated with decreased levels of prostaglandins (PGs) and increased levels of leukotrienes (LTs) in the perilymph. Pretreatment with LT inhibitor was found to prevent salicylate ototoxicity. Other studies demonstrated that salicylate ototoxicity is associated with decreased cochlear blood flow, reversible changes in cochlear outer hair cells, and decreased otoacoustic emissions. The purpose of our study was to determine the effect of LT blocker (Sch 37224) on transient-evoked otoacoustic emissions (TEOAEs) in salicylate or LT ototoxicity. Chinchillas were divided into 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 leukotriene) application on the RWM, with (Group 3) and without (Group 4) 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 blocker. There was no significant change in TEOAEs in the control group. Salicylate ototoxicity appears to be mediated by the elevated levels of leukotrienes as a consequence of cyclooxygenase inhibition. This study also provides further evidence that the site of action in salicylate ototoxicity is the outer hair cell.
Division of Otolaryngology--Head and Neck Surgery, Loma Linda University Medical Center, California, USA.
J
J
Arruda
T T
TT
Jung
D G
DG
McGann
D000161:Acoustic Stimulation; D000818:Animals; D002682:Chinchilla; D003051:Cochlea / Q000187:drug effects*; D006198:Hair Cells, Auditory / Q000187:drug effects; D015289:Leukotrienes / Q000494:pharmacology*; D012459:Salicylates / Q000009:adverse effects* / Q000378:metabolism / Q000494:pharmacology*
D015289:Leukotrienes; D012459:Salicylates