Bielefeld Eric C, Hu Bo Hua, Harris Kelly Carney, Henderson Donald
Department of Communicative Disorders and Sciences, Center for Hearing and Deafness, State University of New York at Buffalo, 137 Cary Hall, 3435 Main Street, Buffalo, NY 14214, USA.
Hear Res. 2005 Sep;207(1-2):35-42. doi: 10.1016/j.heares.2005.03.025.
Superoxide has been implicated as a contributing factor to cochlear pathology from a number of sources, including noise and ototoxic drugs. The effects of NADPH oxidase-dependent superoxide on the cochlea were investigated in the current study using paraquat (PQ). PQ is a toxic herbicide that causes tissue damage by generating superoxide through reduction of molecular oxygen in a reaction catalyzed by NADPH oxidase. The current study examined the effects of round window PQ administration on inferior colliculus (IC) evoked potential thresholds (EVP) and hair cell damage. Using implanted IC electrodes, chinchillas were tested for IC EVP thresholds before and after PQ exposure. Ears were exposed to PQ at one of four concentrations: 10, 5, 3 mM, and vehicle control. Thresholds were increased in a dose-dependent manner, and peaked between one and seven days post-exposure. Thresholds then showed a small amount of recovery before reaching PTS by Day 22. Outer and inner hair cell losses were consistent with PTS. The similarities between PQ ototoxicity and noise-induced hearing loss suggest the possibility of similar biochemical pathways involving superoxide.
超氧化物已被认为是包括噪声和耳毒性药物在内的多种因素导致耳蜗病变的一个促成因素。在本研究中，使用百草枯（PQ）研究了烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶依赖性超氧化物对耳蜗的影响。PQ是一种有毒除草剂，通过在NADPH氧化酶催化的反应中还原分子氧产生超氧化物，从而导致组织损伤。本研究考察了经圆窗给予PQ对下丘（IC）诱发电位阈值（EVP）和毛细胞损伤的影响。使用植入的IC电极，在暴露于PQ之前和之后对栗鼠的IC EVP阈值进行测试。将耳朵暴露于四种浓度之一的PQ：10、5、3 mM，以及溶剂对照。阈值以剂量依赖性方式增加，并在暴露后1至7天达到峰值。然后，阈值在第22天达到永久性阈移（PTS）之前有少量恢复。外毛细胞和内毛细胞损失与PTS一致。PQ耳毒性与噪声性听力损失之间的相似性表明，涉及超氧化物的生化途径可能相似。
