Investigating the mechanisms of liver injury in zebrafish induced by polystyrene microplastics and...

As emerging environmental pollutants, microplastics (MPs) are increasingly prevalent and often coexist with endocrine-disrupting chemicals (EDCs), posing combined toxic threats to aquatic organisms. In this study, zebrafish (Danio rerio) were exposed to polystyrene (PS) microplastics and 17α-methyltestosterone (MT), individually or in combination, for 21 d to systematically evaluate their toxic effects on the gut-liver axis. The results showed that combined exposure to MT and PS significantly altered the composition of the intestinal microbiota, leading to a notable increase in pathogenic bacteria. The harmful metabolites produced by these bacteria jointly induced intestinal inflammation, characterized by upregulated inflammation-related genes and downregulated intestinal barrier-related genes, leading to reduced villus height and abnormal goblet cell proliferation. These metabolites entered the liver via the bloodstream, where they activated the Toll-like receptor signaling pathway, elevated immune-related gene expression, and increased the activities of liver enzymes (ALT and AST), resulting in marked hepatic inflammation and apoptosis. Further analysis revealed that apoptosis was accompanied by lipid vacuolization and mitochondrial damage in hepatocytes, indicating significant liver dysfunction. This study provides an indepth investigation of the liver-gut axis and demonstrates that co-exposure to MT and PS induces more severe hepatic and intestinal injury than exposure to either substance alone. The findings highlight the critical roles of the gut microbiota and the liver-gut axis in endocrine disrupting chemical induced hepatotoxicity, offering scientific evidence for evaluating the combined toxic effects of microplastics and endocrine disruptors.