EFFECT OF LEUKOTRIENE INHIBITOR ON SALICYLATE INDUCED MORPHOLOGIC CHANGES OF ISOLATED COCHLEAR OUTER HAIR-CELLS

Our previous studies have shown that salicylate ototoxicity is associa ted with decreased levels of prostaglandins (PGs) and increased levels of leukotrienes (LTs) in the perilymph. Other studies have demonstrat ed that salicylate ototoxicity is associated with decreased cochlear b lood flow, reversible changes in isolated cochlear outer hair cells (O HCs), and decreased otoacoustic emission. We have shown that pretreatm ent with an LT inhibitor prevents salicylate induced hearing loss, a d ecrease in cochlear blood flow and changes in otoacoustic emissions. T he objectives of the current study were to determine the effect of exp osure of salicylate and LTs on the morphology of isolated OHSc and to determine the effect of LT inhibitors on salicylate induced morphologi c changes of isolated OHCs. Isolated OHCs from chinchilla cochlea were exposed to different test solutions. The groups included sodium salic ylate (10 mM) with or without pretreatment with an LT inhibitor (L-663 ,536, 30 mu M), 0.1 or 1.0 mu M solution of LTC4, LTD4, LTE4, and two control solutions, standard bathing solution (SBS) or leukotriene inhi bitor alone: Osomolality of all solutions were kept al 305 +/- 5 mmolk g(-1). The OHCs were observed under an inverted microscope. Images wer e stored onto a computer and analyzed later. OHCs exposed to the salic yalate developed a decrease in mean cell length. The exposure of OHCs to LTC4, LTD4, and LTE4 also demonstrated a similar decrease in mean c ell length. Cells in the control SBS or LT inhibitor alone groups did not show any change. OHCs exposed to salicylate in the presence of the LT inhibitor did not exhibit morphologic changes. This study suggest that arachidonic acid metabolites, especially an increase in the conce ntration of LTs, seem to play an important role in the pathogenesis of salicylate ototoxicity.