Combined heavy metals (As and Pb) affects antioxidant status and lipid metabolism in zebrafish (Danio rerio)

The potential risk of coexistence of mixed heavy metals in the aquatic environment has increased with the development of technology. Lead (Pb) and arsenic (As) are among the most widely applied heavy metals, whose single toxicity has been extensively investigated, but their combined toxicity has been reported relatively rarely. In this study, different concentrations of Pb (40 μg/L, 4 mg/L), As (32 μg/L, 3.2 mg/L) and their combinations (40 μg/L + 32 μg/L, 4 mg/L + 3.2 mg/L) were set up for 30 days to establish a heavy metal exposure model in zebrafish. Pathological sections, biochemical parameters and gene expression analysis were used to assess the toxicity effects of oxidative damage and lipid metabolism in the liver. Our results showed that combined exposure of As and Pb resulted in elevated ROS and MDA levels and upregulated expression of genes related to the Nrf2-Keap1/Are signaling pathway in female zebrafish, causing enhanced oxidative stress. Moreover, mixture of As and Pb was able to cause abnormal upregulation of lipid metabolism-related genes and reduced activity of fatty acid synthase (FAS) in the liver of female zebrafish. The abnormal decrease of carnitine palmitoyl transferase (CPT-1) and gene cpt1a in males were also observed. These results contributed to hepatic Triglyceride (TG) excessive accumulation, ultimately triggering a disturbance of lipid metabolism. These findings indicated that chronic exposure to As and Pb was capable of producing adverse effects on oxidative stress and lipid metabolism in fish in a sex-specific manner. This study provides new perspective for evaluating the combined effects of heavy metals in the aquatic environment.