Impairment of bile acid metabolism and altered composition by lead and copper in Bufo gargarizans tadpoles

Lead (Pb) and copper (Cu) are two common heavy metal contaminants in environments, and liver is recognized as one of the main target organs for toxicity of Pb and Cu in animal organisms. Bile acids play a critical role in regulating hepatic metabolic homeostasis by activating farnesoid X receptor (Fxr). However, there were few studies on the interactions between bile acids and liver pathology caused by heavy metals. In this work, the histopathological changes, targeted metabolome and transcriptome responses in the liver of Bufo gargarizans tadpoles to Pb and/or Cu were examined. We found that exposure to Pb and/or Cu altered the hepatic bile acid profile, resulting in increased hydrophobicity and toxicity of the bile acid pool. And the expression of genes involved in bile acid metabolism and their downstream signaling pathways in the liver were significantly altered by Pb and/or Cu exposure. The alteration of bile acid profiles and the expression of genes related to bile acid metabolism might induce oxidative stress and inflammation, ultimately inducing hepatocyte injury observed in the histological sections. To our knowledge, this is the first study to provide histological, biochemical, and molecular evidence for establishing the link between Pb and Cu exposure, disturbances in hepatic bile acid metabolism, and liver injury.