Nodularin induced oxidative stress contributes to developmental toxicity in zebrafish embryos

Nodularin (NOD) is a kind of cyanobacterial toxins. It is of concern due to elicit severe genotoxicity in humans and animals. The comprehensive evaluation of NOD-induced adverse effects in living organisms is urgently needed. This study is aimed to report the developmental toxicity and molecular mechanism using zebrafish embryos exposed to NOD. The embryonic toxicity induced by NOD is demonstrated by inhibition of embryo hatching, increase in mortality rate, abnormal heart rate, embryonic malformation as well as defects in angiogenesis and common cardinal vein remodeling. NOD triggered a decreased rate of angiogenesis through inhibiting endothelial cells migration. NOD induced embryonic cell apoptosis and DNA damage, which can be alleviated by antioxidant N-acetyl-L-cysteine. NOD significantly caused oxidative damage as indicated by changes in reactive oxygen species, superoxide dismutase, catalase, glutathione and malondialdehyde. NOD also altered the expression of vascular development-genes (DLL4, CDH5, VEGFA, VEGFC) and apoptosis-related genes (BAX, BCL-2, P53, CASPASE 3). Taken together, NOD induced adverse effect on zebrafish embryos development, which may be associated with oxidative stress and apoptosis through the activation of P53-BAX/BCL-2-CASPASE 3-mediated pathway.