Abstract
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.
Highlights
Indirubin is the an active compound of Chinese herb of indigo blue, which can be used for the treatment of chronic diseases such as chronic myelogenous leukemia, and hepatitis, influenza, and encephalitis (Han, 1994; Wang et al, 2014; Gaboriaud-Kolar et al, 2015)
Zebrafish have been widely accepted as an ideal alternative vertebrate animal model for in vitro assessment of toxicity of chemicals, organic pollutants, and nanoparticles.(Teraoka et al, 2003; Veldman and Lin, 2008)
The transgenic zebrafish lines are labeled with the GFP in liver, heart, blood vessels or immune cells
Summary
Indirubin is the an active compound of Chinese herb of indigo blue, which can be used for the treatment of chronic diseases such as chronic myelogenous leukemia, and hepatitis, influenza, and encephalitis (Han, 1994; Wang et al, 2014; Gaboriaud-Kolar et al, 2015). Previous researches have shown that indirubin and its derivatives possessed many biological activities, including anticancer (Ichimaru et al, 2015; Zhang et al, 2015), anti-inflammatory (Mok et al, 2014; Kwok et al, 2016), anti-leukemia, and antivirus effects. The targets of indirubin and its derivatives have been widely studied. Indirubin and its derivatives act as potent inhibitors of CDKs (CDK1 and CDK2) or GSK3 (GSK-3a and GSK3b) (Blazevic et al, 2015; Gaboriaud-Kolar et al, 2015; Saravanan et al, 2019).
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