Exposure to environmental toxins may be responsible for
biliary atresia. The focus of this study was to investigate the effect of
biliatresone on the development of the hepatobiliary system in mice. We successfully synthesized
biliatresone with a purity of 98% and confirmed its biliary toxicity. Exposure to high doses of
biliatresone caused abortion or death in pregnant mice. Neonatal mice injected with
biliatresone developed clinical signs of biliary obstruction, and dysplasia or the absence of extrahepatic biliary tract lumen, which confirmed the occurrence of
biliary atresia. In the portal tract of
biliary atresia mice, signs of infiltration of inflammatory cells and
liver fibrosis were observed. The signature of extrahepatic biliary gene expression in these mice mainly involved the cell adhesion process, and hepatic
RNA-seq was highly linked to transcriptional evidence of oxidative stress. When compared with the control group, hepatic
glutathione levels were markedly reduced after
biliatresone injection. Taken together, these data confirm that
biliatresone causes severe developmental abnormalities of the hepatobiliary system in mice. Furthermore, decreased levels of
glutathione may play a mechanistic role in the pathogenesis of
liver fibrosis in
biliatresone-induced experimental
biliary atresia.