State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, Ministry of Education, College of Life Science, Nankai University, Tianjin, 300071, China.
Tianjin Key Laboratory of Molecular Drug Research, College of Pharmacy, Nankai University, Tianjin, 300071, China.
Cardiovasc Toxicol. 2021 Jan;21(1):29-41. doi: 10.1007/s12012-020-09591-5. Epub 2020 Jul 10.
Increased application of the pyrethroid insecticide deltamethrin has adverse effects on the cardiac system and neurobehavior on the non-target organisms, which has raised the public's attention. Because of spermidine and melatonin considered to have cardioprotective and neuroprotective characteristics, zebrafish were utilized as the model organism to explore the protective effects of spermidine and melatonin against deltamethrin-induced toxicity. We tested the neurobehavior of zebrafish larvae through a rest/wake behavior assay, and evaluated the levels of the expression of Scn5lab, gata4, nkx2.5, hcrt, hcrtr, and aanat2 by qRT-PCR. Besides that cmlc2 was evaluated by whole-mount in situ hybridization. Results have shown that compared with control group, 0.025 mg/L deltamethrin could significantly disturb the cardiac development, downregulating the expression of Scn5lab and transcriptional factors gata4 and nkx2.5, disturbing cardiac looping, resulting in defects in cardiac morphology and function. Moreover, deltamethrin could alter the expression levels of rest/wake genes and cause hyperactivity in zebrafish larvae. Besides, compared with deltamethrin group, the exogenous 0.01 mg/L spermidine and 0.232 mg/L melatonin could significantly rescue the adverse effects of deltamethrin on the cardiac system and neurobehavior in zebrafish. This indicated that spermidine and melatonin have neuroprotective and cardioprotective effects against deltamethrin-induced adverse effects in zebrafish.
拟除虫菊酯杀虫剂溴氰菊酯的应用增加对非靶标生物的心脏系统和神经行为有不良影响，这引起了公众的关注。由于腐胺和褪黑素被认为具有心脏保护和神经保护特性，因此使用斑马鱼作为模式生物来探索腐胺和褪黑素对溴氰菊酯诱导的毒性的保护作用。我们通过休息/唤醒行为测定法测试了斑马鱼幼虫的神经行为，并通过 qRT-PCR 评估了 Scn5lab、gata4、nkx2.5、hcrt、hcrtr 和 aanat2 的表达水平。此外，通过全胚胎原位杂交评估了 cmlc2。结果表明，与对照组相比，0.025mg/L 的溴氰菊酯可显著干扰心脏发育，下调 Scn5lab 及转录因子 gata4 和 nkx2.5 的表达，干扰心脏环化，导致心脏形态和功能缺陷。此外，溴氰菊酯可改变休息/唤醒基因的表达水平并导致斑马鱼幼虫过度活跃。此外，与溴氰菊酯组相比，外源 0.01mg/L 腐胺和 0.232mg/L 褪黑素可显著挽救溴氰菊酯对斑马鱼心脏系统和神经行为的不良影响。这表明腐胺和褪黑素对斑马鱼具有神经保护和心脏保护作用，可对抗溴氰菊酯诱导的不良影响。
