St Mary's College of Maryland, Department of Biology, 18952 E. Fisher Road, St Mary's City, MD 20686, USA.
J Appl Toxicol. 2010 Aug;30(6):536-41. doi: 10.1002/jat.1523.
In recent years, fish models have become popular for investigations of ototoxic agents. However, the vast majority of such studies have focused on anatomical changes in lateral line hair cells after drug administration. Using the goldfish (Carassius auratus), we confirm that the acquisition of auditory evoked potentials offers a rapid and non-invasive method for quantifying ototoxin-induced changes in hearing sensitivity. Gentamicin (100 mg ml(-1)) was the drug of choice as it is a well-studied human ototoxin. Auditory threshold elevation was observed between 300 and 600 Hz and was accompanied by significant reductions in hair cell ciliary bundle densities in specific regions of the utricle and saccule. The correlations between structure and function suggest that differential susceptibility of sensory hair cells to acute gentamicin treatment underlies the frequency-specific elevation of auditory thresholds. We propose that fish auditory systems should be used alongside the lateral line, for the assessment of ototoxicity in new-developed drugs.
近年来,鱼类模型已成为研究耳毒性药物的热门选择。然而,绝大多数此类研究都集中在药物给药后侧线毛细胞的解剖结构变化上。我们使用金鱼(Carassius auratus)证实,听觉诱发反应的获取提供了一种快速、非侵入性的方法,可定量评估耳毒性物质引起的听力敏感性变化。庆大霉素(100mgml(-1))是一种选择药物,因为它是一种研究充分的人类耳毒素。在 300-600Hz 之间观察到听觉阈值升高,并且伴随着在特定的耳石和囊斑区域毛细胞纤毛束密度显著降低。结构与功能之间的相关性表明,感觉毛细胞对急性庆大霉素治疗的不同敏感性是听觉阈值频率特异性升高的基础。我们建议在新开发的药物中,应将鱼类听觉系统与侧线一起用于评估耳毒性。