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.
The Institute of Robotics and Automatic Information System, Tianjin Key Laboratory of Intelligent Robotics, Nankai University, Tianjin 300350, China.
Ecotoxicol Environ Saf. 2021 Oct 15;223:112555. doi: 10.1016/j.ecoenv.2021.112555. Epub 2021 Jul 28.
As a highly effective plant hormone, the overuse of 6-benzylaminopurine (6-BA) may pose potential threats to organisms and the environment. Melatonin is widely known for its regulation of sleep rhythm, and it also shows a beneficial effect in a variety of adverse situations. In order to investigate the harm of 6-BA to vertebrates and whether melatonin can reverse the toxicity induced by 6-BA, we analyzed the circadian rhythm and cardiovascular system of zebrafish, and further clarified the role of the thyroid endocrine system. The exposure of well-developed embryos started at 2 hpf, then 6-BA and/or melatonin were carried out. The results indicated that 6-BA disturbed the rhythmic activities of the larvae, increased wakefulness, correspondingly reduced their rest, and induced disrupted clock gene expression. Video analysis and qRT-PCR data found that zebrafish under 6-BA exposure showed obvious cardiovascular morphological abnormalities and dysfunction, and the mRNA levels of cardiovascular-related genes (nkx2.5, gata4, myl7, vegfaa and vegfab) were significantly down-regulated. In addition, altered thyroid hormone content and hypothalamus-pituitary-thyroid (HPT) axis-related gene expression were also clearly observed. 1umol/L of melatonin had little effect on zebrafish, but its addition could significantly alleviate the circadian disturbance and cardiovascular toxicity caused by 6-BA, and simultaneously played a regulatory role in thyroid system. Our research revealed the adverse effects of 6-BA on zebrafish larvae and the protective role of melatonin in circadian rhythm, cardiovascular and thyroid systems.
作为一种高效的植物激素，6-苄基氨基嘌呤（6-BA）的过度使用可能对生物和环境构成潜在威胁。褪黑素以调节睡眠节律而闻名，它在各种不利情况下也表现出有益的效果。为了研究 6-BA 对脊椎动物的危害，以及褪黑素是否能逆转 6-BA 引起的毒性，我们分析了斑马鱼的昼夜节律和心血管系统，并进一步阐明了甲状腺内分泌系统的作用。从 2 hpf 开始对发育良好的胚胎进行暴露，然后进行 6-BA 和/或褪黑素处理。结果表明，6-BA 扰乱了幼虫的节律活动，增加了觉醒时间，相应减少了休息时间，并诱导时钟基因表达紊乱。视频分析和 qRT-PCR 数据发现，暴露于 6-BA 的斑马鱼表现出明显的心血管形态异常和功能障碍，与心血管相关的基因（nkx2.5、gata4、myl7、vegfaa 和 vegfab）的 mRNA 水平显著下调。此外，还明显观察到甲状腺激素含量和下丘脑-垂体-甲状腺（HPT）轴相关基因表达的改变。1umol/L 的褪黑素对斑马鱼几乎没有影响，但它的添加可以显著缓解 6-BA 引起的昼夜节律紊乱和心血管毒性，并同时对甲状腺系统发挥调节作用。我们的研究揭示了 6-BA 对斑马鱼幼虫的不良影响，以及褪黑素在昼夜节律、心血管和甲状腺系统中的保护作用。
