Developmental toxicity assay of xanthatin in zebrafish embryos.

Xanthatin (XAN), a xanthanolide sesquiterpene lactone, isolated from Chinese herb, Xanthium strumarium L, has various pharmacological activities, such as antitumor activity and anti-inflammatory. However, little is known about its potential toxicity and the mechanism. Here, zebrafish model was used to study the developmental toxicity in vivo. Our results indicated that xanthatin increased the mortality and led to the morphological abnormalities including pericardial edema, yolk sac edema, curved body shape and hatching delay. Furthermore, xanthatin damaged the normal structure and/or function of heart, liver, immune and nervous system. ROS elevation and much more apoptosis cells were observed after xanthatin exposure. Gene expression results showed that oxidative stress-related genes nrf2 was inhibited, while oxidative stress-related genes (keap1 and nqo1) and apoptotic genes (caspase3, caspase9 and p53) were increased after xanthatin exposure. Mitophagy related genes pink1 and parkin, and wnt pathway (ß-catenin, wnt8a and wnt11) were significantly increased after xanthatin exposure. Taken together, our finding indicated that xanthatin induced developmental toxicity, and the ROS elevation, apoptosis activation, dysregulation of mitophagy and wnt pathways were involved in the toxicity caused by xanthatin.

Developmental toxicity induced by chelerythrine in zebrafish embryos via activating oxidative stress and apoptosis pathways.

Chelerythrine (CHE), a natural benzophenanthridine alkaloid, possesses various biological and pharmacological activities, such as antimicrobial, antitumor and anti-inflammatory effects. However, its adverse side effect has not been fully elucidated. Therefore, this study was designed to investigate the developmental toxicity of CHE in zebrafish. We found that CHE could lead to a notably increase of the mortality and malformation rate, while lead to reduction of the hatching rate and body length. CHE also could affect the normal developing processes of the heart, liver and phagocytes in zebrafish. Furthermore, the reactive oxygen species (ROS) and apoptosis levels were notably increased. In addition, the mRNA expressions of genes (bax, caspase-9, p53, SOD1, KEAP1, TNF-α, STAT3 and NF-κB) were significantly increased, while the bcl2 and nrf2 were notably inhibited by CHE. These results indicated that the elevation of ROS and apoptosis were involved in the developmental toxicity induced by CHE. In conclusion, CHE exhibits a developmental toxicity in zebrafish, which helps to understand the potential toxic effect of CHE.