Department of Biotechnology, Indian Institute of Technology Hyderabad (IITH), Kandi, Sangareddy, Telangana, 502285, India.
Macromolecular Structural Biology Lab, Department of Biotechnology, Indian Institute of Technology Hyderabad (IITH), Kandi, Sangareddy, Telangana, 502285, India.
Chemosphere. 2021 Mar;266:128930. doi: 10.1016/j.chemosphere.2020.128930. Epub 2020 Nov 12.
The widespread use of triclosan in personal care products as an antimicrobial agent is leading to its alarming tissue-bioaccumulation including human brain. However, knowledge of its potential effects on the vertebrate nervous system is still limited. Here, we hypothesized that sublethal triclosan concentrations are potent enough to alter motor neuron structure and function in zebrafish embryos exposed for prolonged duration. In this study, zebrafish embryos were used as vertebrate-animal model. Prolonged exposure (up to 4 days) of 0.6 mg/L (LC 96 h) and 0.3 mg/L (<LC Sublethal) triclosan produced aberrations in motor neuron innervations in skeletal muscles and reduced touch-evoked escape response in zebrafish larvae. This suggests motor dysfunction in treated embryos. To further explore the mechanisms of triclosan induced neurotoxicity, we determined the enzyme activity of acetylcholinesterase (AChE) and the expression of acetylcholinesterase (ache), myelin basic protein (mbp) and synapsin IIa (syn2a) genes which play an important role in the neural development and synaptic transmission. The ache and syn2a genes were down-regulated in triclosan treated larvae without any significant changes in mbp gene expression. At functional level, we observed a decrease in the AChE activity. Furthermore, docking results showed that triclosan can form a stable interaction with binding pocket of AChE and perhaps it can compete with natural acetylcholine for direct binding to AChE thereby inhibiting it and affecting cholinergic transmission. Therefore, triclosan can be regarded as a neurotoxic agent even at sublethal concentrations. Overall, the growing toxicological evidence against triclosan including ours suggest caution in its widespread use.
三氯生作为一种抗菌剂被广泛应用于个人护理产品，导致其在组织中惊人的生物蓄积，包括人类大脑。然而，其对脊椎动物神经系统潜在影响的知识仍然有限。在这里，我们假设亚致死浓度的三氯生足以改变斑马鱼胚胎暴露于延长时间后的运动神经元结构和功能。在这项研究中，斑马鱼胚胎被用作脊椎动物模型。延长暴露（长达 4 天）于 0.6mg/L（LC96h）和 0.3mg/L（<LC 亚致死）三氯生会导致斑马鱼幼虫骨骼肌运动神经元支配异常，并降低触诱发应性逃避反应。这表明处理胚胎中的运动功能障碍。为了进一步探讨三氯生诱导神经毒性的机制，我们测定了乙酰胆碱酯酶（AChE）的酶活性以及乙酰胆碱酯酶（ache）、髓鞘碱性蛋白（mbp）和突触素 IIa（syn2a）基因的表达，这些基因在神经发育和突触传递中起着重要作用。在三氯生处理的幼虫中，ache 和 syn2a 基因下调，而 mbp 基因表达没有明显变化。在功能水平上，我们观察到 AChE 活性降低。此外，对接结果表明，三氯生可以与 AChE 的结合口袋形成稳定的相互作用，并且可能与天然乙酰胆碱竞争，直接结合 AChE，从而抑制它并影响胆碱能传递。因此，即使在亚致死浓度下，三氯生也可以被视为神经毒性剂。总的来说，包括我们在内的越来越多的关于三氯生的毒理学证据表明，在广泛使用时应谨慎。
