The NTCP receptor inhibitor Ezetimibe reduces the toxicity of a-amanitin: in vitro and in vivo study.
Background and Aims: To verify the protective effect of Ezetimibe, an sodium taurocholate co-transporting polypeptide (NTCP) inhibitor, on a-amanitin poisoning in vitro and in vivo by inhibiting NTCP to prevent a-amanitin into hepatocytes. Approach and Results: In animal experiments, the survival rate was significantly improved in the treatment group. The pathomorphological characteristics of liver and kidney in the treatment group were significantly improved. In cell experiments,The cell viability of the treatment group was significantly improved, and the expression of NTCP in the treatment group was significantly decreased by immunofluorescence. In molecular docking simulations, we demonstrated the potential of NTCP to bind Ezetimibe and a-amanitin, respectively. Transcriptomics in high-throughput sequencing was used to detect the differential metabolic genes between a-amanitin poisoning group and the treatment group, and signal pathway enrichment was used to analyze the significantly different signal pathways. Conclusions: Ezetimibe, as an inhibitor of NTCP, can reduce the entry of a-amanitin into hepatocytes to play a protective role and improve the cell viability and survival rate of mice. Overall design: Compare the control group using high-throughput sequencing Differences in mRNA gene expression in L-02 cell lines between  a-amanitin poisoning group and Ezetimibe treatment group after poisoning