School of Life Science, Nanchang University, Nanchang 330031, China.
Int J Mol Sci. 2022 Apr 26;23(9):4783. doi: 10.3390/ijms23094783.
Selenium is an essential trace element for humans and other vertebrates, playing an important role in antioxidant defense, neurobiology and reproduction. However, the toxicity of excessive selenium has not been thoroughly evaluated, especially for the visual system of vertebrates. In this study, fertilized zebrafish embryos were treated with 0.5 µM L-selenomethionine to investigate how excessive selenium alters zebrafish eye development. Selenium-stressed zebrafish embryos showed microphthalmia and altered expression of genes required for retinal neurogenesis. Moreover, ectopic proliferation, disrupted mitochondrial morphology, elevated ROS-induced oxidative stress, apoptosis and ferroptosis were observed in selenium-stressed embryos. Two antioxidants-reduced glutathione (GSH) and N-acetylcysteine (NAC)-and the ferroptosis inhibitor ferrostatin (Fer-1) were unable to rescue selenium-induced eye defects, but the ferroptosis and apoptosis activator cisplatin (CDDP) was able to improve microphthalmia and the expression of retina-specific genes in selenium-stressed embryos. In summary, our results reveal that ferroptosis and apoptosis might play a key role in selenium-induced defects of embryonic eye development. The findings not only provide new insights into selenium-induced cellular damage and death, but also important implications for studying the association between excessive selenium and ocular diseases in the future.
硒是人类和其他脊椎动物必需的微量元素，在抗氧化防御、神经生物学和生殖等方面发挥着重要作用。然而，过量硒的毒性尚未得到彻底评估，特别是对脊椎动物的视觉系统。在这项研究中，用 0.5µM L-硒代蛋氨酸处理受精斑马鱼胚胎，以研究过量硒如何改变斑马鱼眼睛发育。受硒胁迫的斑马鱼胚胎表现出小眼症，并改变了视网膜神经发生所需基因的表达。此外，在受硒胁迫的胚胎中观察到细胞异位增殖、线粒体形态破坏、ROS 诱导的氧化应激升高、细胞凋亡和铁死亡。两种抗氧化剂——还原型谷胱甘肽 (GSH) 和 N-乙酰半胱氨酸 (NAC)——以及铁死亡抑制剂 Fer-1 均不能挽救硒诱导的眼睛缺陷，但铁死亡和细胞凋亡激活剂顺铂 (CDDP) 能够改善受硒胁迫的胚胎小眼症和视网膜特异性基因的表达。总之，我们的结果表明铁死亡和细胞凋亡可能在硒诱导的胚胎眼睛发育缺陷中发挥关键作用。这些发现不仅为研究硒诱导的细胞损伤和死亡提供了新的见解，而且对未来研究过量硒与眼部疾病之间的关系具有重要意义。
