School of Chemistry, Guangzhou Key Laboratory of Analytical Chemistry for Biomedicine, South China Normal University, Guangzhou 510006, China.
Key Laboratory of Microbial Technology for Industrial Pollution Control of Zhejiang Province, College of Environment, Zhejiang University of Technology, Hangzhou 310014, China.
Pestic Biochem Physiol. 2022 Jul;185:105136. doi: 10.1016/j.pestbp.2022.105136. Epub 2022 Jun 3.
Paclobutrazol is a widely used chiral plant growth regulator and its enantioselective toxicity in aquatic organisms is less explored till now. Herein, the enantioselective neurotoxicity of paclobutrazol mediated by oxidative stress in zebrafish were investigated. The oxidative stress parameters and neurotoxic biomarkers changed significantly in each exposure group, and paclobutrazol showed enantioselective toxicity in zebrafish. Firstly, (2R, 3R)-paclobutrazol exhibited a stronger oxidative stress in zebrafish than (2S, 3S)-enantiomer (P < 0.05). Then, activities of acetylcholinesterase, calcineurin, and total nitric oxide synthase in (2R, 3R)-paclobutrazol treatments were 0.61-0.89, 1.24-1.53, and 1.21-1.35-fold stronger (P < 0.05) than those in (2S, 3S)-enantiomer treatments, respectively. Next, the content variations of four neurotransmitters in zebrafish exposed to (2R, 3R)-paclobutrazol were significantly larger than those in (2S, 3S)-enantiomer treatments (P < 0.05). Moreover, (2R, 3R)-paclobutrazol had stronger binding with the receptors than (2S, 3S)-enantiomer through molecular docking. The integrated biomarker response values further demonstrated that (2R, 3R)-paclobutrazol showed stronger toxicity to zebrafish than (2S, 3S)-enantiomer. Furthermore, the neurotoxicity of paclobutrazol can be interpreted as the mediating effect of oxidative stress in zebrafish through correlation analysis, and an adverse outcome pathway for the nervous system in zebrafish induced by paclobutrazol was proposed. This work will greatly extend our understanding on the enantioselective toxic effects of paclobutrazol in aquatic organisms.
多效唑是一种广泛使用的手性植物生长调节剂，其对水生生物的对映选择性毒性至今仍未得到充分研究。本研究以斑马鱼为模型，探讨了多效唑通过氧化应激介导的对映选择性神经毒性。结果表明，各暴露组的氧化应激参数和神经毒性生物标志物均发生显著变化，多效唑对斑马鱼表现出对映选择性毒性。首先，（2R，3R）-多效唑在斑马鱼体内引起的氧化应激强于（2S，3S）-对映体（P < 0.05）。随后，（2R，3R）-多效唑处理组的乙酰胆碱酯酶、钙调神经磷酸酶和总一氧化氮合酶的活性分别比（2S，3S）-对映体处理组高 0.61-0.89、1.24-1.53 和 1.21-1.35 倍（P < 0.05）。接着，暴露于（2R，3R）-多效唑的斑马鱼中四种神经递质的含量变化明显大于（2S，3S）-对映体处理组（P < 0.05）。此外，分子对接结果表明，（2R，3R）-多效唑与受体的结合能力强于（2S，3S）-对映体。整合生物标志物响应值进一步表明，（2R，3R）-多效唑对斑马鱼的毒性强于（2S，3S）-对映体。此外，通过相关性分析，多效唑对斑马鱼的神经毒性可以解释为氧化应激的介导作用，并提出了多效唑诱导斑马鱼神经系统不良结局的途径。这项工作将极大地扩展我们对手性植物生长调节剂多效唑在水生生物中对映选择性毒性效应的认识。
