Fenoxycarb induces cardiovascular, hepatic, and pancreatic toxicity in zebrafish larvae via ROS production, excessive inflammation, and apoptosis

Fenoxycarb, a carbamate insecticide, functions as a juvenile hormone agonist to inhibit pests, and its detection in aquatic environments is concerning because of its widespread application. These concerns have led to ecotoxicological studies on aquatic crustaceans; however, research on the effects of fenoxycarb on the developmental processes of organisms is limited. In the present study, the deleterious effects of fenoxycarb on zebrafish development and the related cellular mechanisms mediating this toxicity were addressed. Exposure to sublethal concentrations of fenoxycarb (0, 0.5, 1, and 2 mg/L) resulted in morphological defects in zebrafish larvae, particularly in the heart region, eyes, and body length. These defects were accompanied by an increase in the number of apoptotic cells and the upregulation of related gene expression. Moreover, fenoxycarb increased ROS production and the number of macrophages, and altered the expression of immune-related genes, thereby inducing inflammation. These results revealed various abnormalities in the heart, vasculature, liver, and pancreas, as confirmed by transgenic models, such as cmlc2:DsRed, fli1a:EGFP, and fabp10a:DsRed;elastase:GFP. These developmental impairments were associated with the altered expression levels of genes involved in the development and function of each organ. These results suggest that fenoxycarb can affect multiple organs through excessive inflammation during development and highlight its potent toxic effects on other non-target organisms.