Affiliation:
1. Ganzhou Key Laboratory for Drug Screening and Discovery, School of Geography and Environmental Engineering Gannan Normal University Ganzhou China
2. Jiangxi Provincial Key Laboratory of Low‐Carbon Solid Waste Recycling, Gannan Normal University Ganzhou China
3. Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Clinical Research Center of the Affiliated Hospital of Jinggangshan University, College of Life Sciences Jinggangshan University Ji'an China
4. Nudear Industry Ganzhou Geotechnech Investigation & Design Group Company Limited Guangzhou China
5. Food College Nanchang University Nanchang China
Abstract
AbstractFlumioxazin is a widely applied herbicide for the control of broadleaf weeds, including aquatic plants. Current evidence suggests 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, the assumption is made that flumioxazin‐induced cardiotoxicity is caused by oxidative stress. To verify whether oxidative stress plays an important role in flumioxazin‐induced cardiotoxicity, we compared the differences in heart phenotype, oxidative stress level, apoptosis, and gene expression between flumioxazin exposure and a normal environment, and we also tested whether cardiotoxicity could be rescued with astaxanthin. The results showed that flumioxazin induced both cardiac malformations and the abnormal gene expression associated with cardiac development. Cardiac malformations included pericardial edema, cardiac linearization, elongated heart, cardiomegaly, cardiac wall hypocellularity, myocardial cell atrophy with a granular appearance, 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. The antioxidant astaxanthin reversed the cardiac malformations, excessive production of reactive oxygen species (ROS), and expression of genes for cardiac developmental and apoptosis regulation induced by flumioxazin. In addition, flumioxazin also activated aryl hydrocarbon receptor (AhR) signaling pathway genes (aryl hydrocarbon receptor 2 [ahr2], cytochrome p450 family subfamily a [cyp1a1], and b [cyp1b1]) and increased the concentration of porphyrins. 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. Environ Toxicol Chem 2023;42:2737–2746. © 2023 SETAC
Funder
National Natural Science Foundation of China
Subject
Health, Toxicology and Mutagenesis,Environmental Chemistry