Oxidative stress contributes to flumioxazin‐induced cardiotoxicity in zebrafish embryos

Abstract

Flumioxazin is a widely applicated herbicide in the control of aquatic plants. Current evidence suggested that flumioxazin could induce cardiac defects (ventricular septal defects) in vertebrates, but the underlining mechanisms remain unclear. Because of the inhibitory effect of flumioxazin on polyphenol oxidase (PPO), the assumption is made that flumioxazin‐induced cardiotoxicity is caused by oxidative stress. The results show that flumioxazin induced cardiac malformations and abnormal gene expression associated with cardiac development. Cardiac malformations include pericardium edema, cardiac linearization, elongated heart, cardiomegaly, cardiac wall hypocellularity, myocardial cell atrophy into granular, and a significant gap between the myocardial intima and the adventitia. An increase in oxidative stress and apoptosis was observed in the cardiac region of zebrafish after exposure to flumioxazin. Antioxidant astaxanthin reversed the cardiac malformations, excessive ROS production and expression of genes for cardiac developmental and apoptosis regulation induced by flumioxazin. In addition, flumioxazin also activated AHR signaling pathway genes (ahr2, cyp1a1, and cyp1b1) and increased porphyrins concentration. In conclusion, the results suggest that excessive ROS production, which could be mediated through AHR, led to apoptosis, contributing to the cardiotoxicity of flumioxazin in zebrafish embryos.