Nicotera Thomas M, Ding Dalian, McFadden Sandra L, Salvemini Daniela, Salvi Richard
Department of Molecular and Cellular Biophysics, Roswell Park Cancer Institute, Buffalo, NY 14214, USA.
Audiol Neurootol. 2004 Nov-Dec;9(6):353-62. doi: 10.1159/000081284. Epub 2004 Oct 1.
Some forms of ototoxicity appear to be mediated primarily by the superoxide radical; however, the exact role the superoxide radical plays in cochlear damage is not well understood because most ototoxic drugs produce multiple reactive oxygen species. To characterize the role of the superoxide radical in cochlear damage and the protective effect of compounds that inactivate superoxide, we treated mouse cochlear organotypic cultures for 24 h with paraquat, an herbicide that produces high levels of superoxide. M40403, a highly specific, nonpeptidyl mimetic of superoxide dismutase, was added to some cultures to inactivate the superoxide radical generated by paraquat. The number of outer hair cells (OHC) and inner hair cells (IHC) systematically decreased with increasing concentration of paraquat (0.01-10 mM). M40403 (10 muM) significantly increased OHC and IHC survival in cultures treated with 0.01-1.0 mM of paraquat. These results suggest that excess production of superoxide radical is a sufficient condition for hair cell loss.
某些形式的耳毒性似乎主要由超氧阴离子介导；然而，超氧阴离子在耳蜗损伤中的确切作用尚未完全明确，因为大多数耳毒性药物会产生多种活性氧。为了阐明超氧阴离子在耳蜗损伤中的作用以及超氧阴离子失活化合物的保护作用，我们用百草枯（一种能产生大量超氧阴离子的除草剂）处理小鼠耳蜗器官型培养物24小时。在一些培养物中加入M40403（一种高度特异性的超氧化物歧化酶非肽模拟物），以失活百草枯产生的超氧阴离子。随着百草枯浓度（0.01 - 10 mM）的增加，外毛细胞（OHC）和内毛细胞（IHC）的数量系统性减少。在使用0.01 - 1.0 mM百草枯处理的培养物中，M40403（10 μM）显著提高了OHC和IHC的存活率。这些结果表明，超氧阴离子产生过多是毛细胞损失的充分条件。
