Wang Rongchun, Liu Kechun, Zhang Yun, Chen Xiqiang, Wang Xue
Key Laboratory for Drug Screening Technology of Shandong Academy of Sciences, Key Laboratory for Biosensor of Shandong Province, Biology Institute, Qilu University of Technology, Shandong Academy of Sciences, Jinan, China.
Front Pharmacol. 2020 Feb 14;11:32. doi: 10.3389/fphar.2020.00032. eCollection 2020.
E804, a derivative of indirubin, have multi-biological activities such as anticancer and anti-inflammatory activities, but little is known about its developmental toxicity. In this study, we investigated the toxicity of E804 on the developments of zebrafish embryos. Our results showed that E804 treatment caused a significant increase of the malformation rate compared with the control groups. Pericardial edema and curved body shape were the most morphological abnormalities observed in E804-treated group. The hatching rates and body length of the zebrafish larvae was significantly decreased in E804-treated groups. E804 also affect the development of heart, liver, phagocytes and vascular formation. Further studies showed that the level of reactive oxygen species was significantly increased. The activity of total superoxide dismutase decreased and the concentration of malondialdehyde were increased. Much more apoptotic cells were detected in E804-treated group, compared with the control. In addition, gene-expression results showed that the pathways of oxidative stress and apoptosis were provoked in E804 treated groups. Taken together, our findings will be helpful to understanding E804-induced developmental toxicity and the underlying mechanism.
E804是靛玉红的衍生物，具有抗癌和抗炎等多种生物活性，但其发育毒性鲜为人知。在本研究中，我们调查了E804对斑马鱼胚胎发育的毒性。我们的结果表明，与对照组相比，E804处理导致畸形率显著增加。心包水肿和身体弯曲是E804处理组中观察到的最常见形态异常。E804处理组中斑马鱼幼虫的孵化率和体长显著降低。E804还影响心脏、肝脏、吞噬细胞的发育和血管形成。进一步研究表明，活性氧水平显著升高。总超氧化物歧化酶活性降低，丙二醛浓度增加。与对照组相比，E804处理组检测到更多凋亡细胞。此外，基因表达结果表明，E804处理组中氧化应激和凋亡途径被激活。综上所述，我们的研究结果将有助于理解E804诱导的发育毒性及其潜在机制。
