Effect of leukotriene inhibitor on salicylate induced morphologic changes of isolated cochlear outer hair cells.
Effect of leukotriene inhibitor on salicylate induced morphologic changes of isolated cochlear outer hair cells.
复制标题
白三烯抑制剂对水杨酸盐诱导的离体耳蜗外毛细胞形态变化的影响。
作者：
T. Jung;J. P. Kim;J. Bunn;D. Davamony;J. Duncan;W. Fletcher
我们以前的研究表明，水杨酸盐耳毒性与外淋巴液中前列腺素（PGs）水平降低和白三烯（LTs）水平升高有关。其他研究表明，水杨酸盐耳毒性与耳蜗血流量减少、孤立耳蜗外毛细胞（OHC）的可逆性变化和耳声发射减少有关。我们已经表明，预处理与LT抑制剂预防水杨酸诱导的听力损失，耳蜗血流量减少和耳声发射的变化。本研究的目的是确定接触水杨酸和LT对分离的OHSc形态的影响，并确定LT抑制剂对水杨酸诱导的分离的OHC形态变化的影响。将来自灰鼠耳蜗的分离的OHC暴露于不同的测试溶液。这些组包括水杨酸钠（10 mM），用或不用LT抑制剂（L-663、536、30 μ M）预处理，0.1或1.0 μ M的LTC 4、LTD 4、LTE 4溶液，以及两种对照溶液，标准洗浴溶液（SBS）或单独的白三烯抑制剂。所有溶液的渗透压均保持在305 +/- 5 mmolkg-1。在倒置显微镜下观察OHC。图像被存储在计算机上，随后进行分析。暴露于水杨酸盐的OHC的平均细胞长度减少。暴露于LTC 4、LTD 4和LTE 4的OHC也表现出平均细胞长度的类似减少。对照SBS或单独LT抑制剂组中的细胞未显示任何变化。在LT抑制剂存在下暴露于水杨酸盐的OHC没有表现出形态学变化。这项研究表明，花生四烯酸代谢产物，特别是LT浓度的增加，似乎在水杨酸盐耳毒性的发病机制中发挥重要作用。
Our previous studies have shown that salicylate ototoxicity is associated with decreased levels of prostaglandins (PGs) and increased levels of leukotrienes (LTs) in the perilymph. Other studies have demonstrated that salicylate ototoxicity is associated with decreased cochlear blood flow, reversible changes in isolated cochlear outer hair cells (OHCs), and decreased otoacoustic emission. We have shown that pretreatment with an LT inhibitor prevents salicylate induced hearing loss, a decrease in cochlear blood flow and changes in otoacoustic emissions. The objectives of the current study were to determine the effect of exposure of salicylate and LTs on the morphology of isolated OHSc and to determine the effect of LT inhibitors on salicylate induced morphologic changes of isolated OHCs. Isolated OHCs from chinchilla cochlea were exposed to different test solutions. The groups included sodium salicylate (10 mM) with or without pretreatment with an LT inhibitor (L-663, 536, 30 microM), 0.1 or 1.0 microM solution of LTC4, LTD4, LTE4, and two control solutions, standard bathing solution (SBS) or leukotriene inhibitor alone. Osomolality of all solutions were kept at 305 +/- 5 mmolkg-1. The OHCs were observed under an inverted microscope. Images were stored onto a computer and analyzed later. OHCs exposed to the salicyalate developed a decrease in mean cell length. The exposure of OHCs to LTC4, LTD4, and LTE4 also demonstrated a similar decrease in mean cell 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 concentration of LTs, seem to play an important role in the pathogenesis of salicylate ototoxicity.