title: Effect of leukotriene inhibitor on cochlear blood flow in salicylate ototoxicity.
abstract: Our previous studies showed that salicylate ototoxicity is associated with decreased levels of vasodilating prostaglandins (PGs) and increased vasoconstricting leukotrienes (LTs) in the perilymph and reduced cochlear blood flow (CoBF). The purpose of this study was to test the hypothesis that leukotriene inhibitor prevents salicylate ototoxicity by preventing abnormal elevation of LT levels in the inner ear, thus averting a decrease in CoBF resulting from abnormal levels of arachidonic acid metabolites in the inner ear. Ototoxicity was induced in chinchillas by either local round window membrane (RWM) application or systemic treatment with salicylate both with and without pretreatment with leukotriene inhibitor (Sch 37224). A moderate reduction in CoBF was documented with both local RWM and systemic treatment with salicylate. Salicylate induced hearing loss and reduction in CoBF were prevented by pretreatment with a leukotriene inhibitor. This study suggests that leukotriene inhibitor prevents salicylate ototoxicity by averting a decrease in CoBF mediated by abnormal levels of arachidonic acid metabolites in the inner ear.
authors.affiliation: Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, Loma Linda University School of Medicine, CA, USA.
authors.forename: T T
authors.initials: TT
authors.lastname: Jung
authors.forename: A L
authors.initials: AL
authors.lastname: Hwang
authors.forename: S K
authors.initials: SK
authors.lastname: Miller
authors.forename: C K
authors.initials: CK
authors.lastname: Rhee
authors.forename: Y S
authors.initials: YS
authors.lastname: Park
mesh_terms: D000818:Animals; D001775:Blood Circulation / Q000187:drug effects*; D002682:Chinchilla; D003051:Cochlea / Q000098:blood supply* / Q000187:drug effects*; D007758:Ear, Inner / Q000098:blood supply* / Q000187:drug effects*; D004432:Ear, Middle / Q000098:blood supply* / Q000187:drug effects*; D005260:Female; D015289:Leukotrienes / Q000378:metabolism*; D008297:Male; D011453:Prostaglandins / Q000378:metabolism; D012405:Round Window, Ear / Q000098:blood supply / Q000187:drug effects; D012459:Salicylates / Q000009:adverse effects* / Q000494:pharmacology*; D020156:Salicylic Acid; D014664:Vasodilation / Q000187:drug effects
chemical_list: D015289:Leukotrienes; D011453:Prostaglandins; D012459:Salicylates; D020156:Salicylic Acid