Paraquat is a widely utilized herbicide in agricultural fields posing a significant impact on human health and the environment due to its potent oxidant properties. Rampant paraquat usage leads to serious health hazards to farmers and the ecosystem, particularly the water bodies. Paraquat exposure can damage dopaminergic neurons causing Parkinson's disease in humans and other animal models. Extensive research has been done regarding the mode of action, pathophysiology and molecular mechanisms of paraquat-induced Parkinson's disease. Meanwhile, the ototoxic effect of paraquat remains poorly understood. Potential ototoxins can cause sensorineural hearing loss, one of the most common sensory disabilities in humans. In this study, we investigated the harmful effects of paraquat on neuromast hair cells in zebrafish larvae, a powerful model organism for auditory research. We treated sub-lethal concentrations (125 μM to 1000 μM) of paraquat to 3 and 4 dpf zebrafish larvae to investigate its ototoxic effects via rheotaxis behavioral assay, neuromast staining and scanning electron microscopy. The behavioral assay findings showed a drastic decline in the rheotaxis behavior in all the concentrations of paraquat-treated larvae. Furthermore, DASPEI neuromast vital staining displayed a dose-dependent reduction in the neuromast hair cells as we increased the paraquat concentration. The scanning electron microscope data revealed the significant shortening of kinociliary length, a decrease in stereociliary density and changes in semilunar peridermal cell morphology signifying the damaging effects of paraquat at the cellular level. Collectively, the behavioral, anatomical and morphological studies highlight the potential ototoxic effects of paraquat on zebrafish neuromast hair cells, further signifying its potential role in causing hearing loss in humans.

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揭示百草枯对斑马鱼幼虫的耳毒性作用


百草枯是一种在农业领域广泛使用的除草剂，由于其强效氧化特性，对人类健康和环境构成重大影响。百草枯的猖獗使用会对农民和生态系统（尤其是水体）造成严重的健康危害。接触百草枯会损害多巴胺能神经元，导致人类和其他动物模型患帕金森病。关于百草枯诱导的帕金森病的作用方式、病理生理学和分子机制，已经进行了广泛的研究。与此同时，人们对百草枯的耳毒性作用仍然知之甚少。潜在的耳毒素会导致感音神经性听力损失，这是人类最常见的感觉障碍之一。在这项研究中，我们研究了百草枯对斑马鱼幼虫神经肥大毛细胞的有害影响，斑马鱼幼虫是一种强大的听觉研究模式生物。我们将亚致死浓度（125 μM 至 1000 μM）的百草枯处理为 3 dpf 和 4 dpf 斑马鱼幼虫，通过流变性行为测定、神经肥大染色和扫描电子显微镜检查其耳毒性作用。行为检测结果显示，在所有浓度的百草枯处理幼虫中，流变性行为急剧下降。此外，DASPEI 神经肥大分子生命体征染色显示，随着百草枯浓度的增加，神经肥大毛细胞呈剂量依赖性减少。扫描电子显微镜数据显示，百草枯的纤毛长度显著缩短，立体纤毛密度降低，半月形周皮细胞形态发生变化，这表明百草枯在细胞水平上的破坏性作用。 总的来说，行为学、解剖学和形态学研究强调了百草枯对斑马鱼神经肥大毛细胞的潜在耳毒性作用，进一步表明了它在导致人类听力损失方面的潜在作用。