Early life stage transient aristolochic acid exposure induces behavioral hyperactivity but not nephrotoxicity in larval zebrafish.
Early life stage transient aristolochic acid exposure induces behavioral hyperactivity but not nephrotoxicity in larval zebrafish.
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早期生命阶段短暂的马兜铃酸暴露诱导行为多动症，但没有斑马鱼幼虫肾毒性。
DOI：
10.1016/j.aquatox.2021.105916
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发表时间：
2021-07-18
期刊：
影响因子：
--
通讯作者：
Dong Q
中科院分区：
文献类型：
--
作者：
Chen J;Kong A;Shelton D;Dong H;Li J;Zhao F;Bai C;Huang K;Mo W;Chen S;Xu H;Tanguay RL;Dong Q
马兜铃酸（AA）是在马兜铃科植物中发现的硝基菲羧酸。人类通过故意服用草药或由于环境污染而无意中暴露于AA。AA因其肾毒性而臭名昭著，然而，很少有研究探讨与AA暴露相关的潜在神经毒性。发育中的神经系统容易受到外源性物质的影响，孕妇接触AA可能会使胎儿处于危险之中。在本研究中，我们使用胚胎斑马鱼模型来评估与AA暴露相关的发育神经毒性。在非致畸性浓度（≤ 4 μM）下，受精后（hpf）8至120小时连续暴露AA导致幼虫活动过度，其特征为在几项行为测定中移动距离增加、活动增加和游泳速度加快。进一步分析显示，8-24 hpf是AA诱导的多动症的最敏感暴露窗口。AA暴露特别增加运动神经元增殖，增加眼睛的凋亡，并导致细胞氧化应激。此外，AA暴露增加幼虫眼睛的大小和扰乱视觉基因的表达。我们的研究，第一次，表明AA是神经毒性的发育斑马鱼的敏感窗口不同，其良好的记录肾毒性。
Aristolochic acids (AA) are nitrophenanthrene carboxylic acids found in plants of the Aristolochiaceae family. Humans are exposed to AA by deliberately taking herbal medicines or unintentionally as a result of environmental contamination. AA is notorious for its nephrotoxicity, however, fewer studies explore potential neurotoxicity associated with AA exposure. The developing nervous system is vulnerable to xenobiotics, and pregnant women exposed to AA may put their fetuses at risk. In the present study, we used the embryonic zebrafish model to evaluate the developmental neurotoxicity associated with AA exposure. At non-teratogenic concentrations (≤ 4 μM), continuous AA exposure from 8 to 120 hours post fertilization (hpf) resulted in larval hyperactivity that was characterized by increased moving distance, elevated activity and faster swimming speeds in several behavioral assays. Further analysis revealed that 8–24 hpf is the most sensitive exposure window for AA-induced hyperactivity. AA exposures specifically increased motor neuron proliferation, increased apoptosis in the eye, and resulted in cellular oxidative stress. In addition, AA exposures increased larval eye size and perturbed the expression of vision genes. Our study, for the first time, demonstrates that AA is neurotoxic to the developmental zebrafish with a sensitive window distinct from its well-documented nephrotoxicity.
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