Synthesis study of biliatresone, a plant isoflavonoid that causes biliary atresia in zebrafish

Objective To observe the effects of biliatresone on the development of biliary system in zebrafish larvae. Methods Biliatresone was synthesized by chemical process, and control groups (DMSO) and different concentrations of biliatresone groups (0.1, 0.15, 0.2 and 0.25 mg/L) were set up. The general and biliary system development of zebrafish larval at 6, 24, 48 h were observed. Results Biliatresone with a purity of 98% were successfully synthesized. No zebrafish died within 48 h in the control group and 0.10 mg/L; with increasing concentrations and prolonged duration of treatment from 0.15 mg/L, the mortality rate of zebrafish gradually increased. The zebrafish died after treatment with 0.25 mg/L biliatresone for 48 h. Treatment with 0.15 mg/L for 48 h or 0.20 mg/L for more than 24 h resulted in severe malformation of zebrafish gallbladder, and the appearance of the gallbladder and other extrahepatic bile ducts were unrecognizable. The fluorescent-labeled fatty acid excretion experiment showed that fluorescence intensity of gallbladders were disappeared and intestine was significantly weakened. Compared with the control group, there was no significant change in the general development of zebrafish in different biliatresone groups. Conclusion Synthetic biliatresone has biliary toxicity and can induces biliary atresia in zebrafish. The in-depth study of biliatresone will provide a new starting point for exploring the pathogenesis of biliary atresia. Key words: Biliatresone; Zebrafish; Biliary atresia; Animal model