Multiview Reveals the Combined Effects of Chiral Pesticide Pydiflumetofen and Cadmium on Glucolipid Metabolism in Zebrafish Liver.

The effects of the chiral fungicide pydiflumetofen (PYD) and the heavy metal cadmium (Cd) on hepatic glucolipid metabolism in zebrafish were investigated. S-PYD was preferentially accumulated in zebrafish, and Cd increased the accumulation of PYD by 1.22-1.78 times depending on the enantiomer. The mitochondria damage, endoplasmic reticulum hyperplasia, hepatic steatosis, the increase of glucose, triglyceride (TG) and oxidative stress, and the significant alterations of the peroxisome proliferator activated receptor signaling pathway revealed glucolipid metabolism disorders in zebrafish liver. R-PYD induced more serious effects than S-PYD. Cd coexposure alleviated these disorders, as evidenced by reduced TG, oxidative markers, PPAR-related genes, and differentially expressed gene counts, and the effects were more significant for R-PYD. Molecular dynamics simulations revealed that Cd destabilized PYD-PPARα binding, showing antagonistic effects. These findings provided new insights for further toxicological investigations and risk assessments of combined pollutions, enhancing the data support for PYD rational use.