Clinical characteristics and potential damage mechanisms of drug-induced liver injury caused by omeprazole

Yu Qiyi; Zhou Rongping; Wang Jiabing

doi:10.3969/j.issn.1672-8157.2025.06.044

Abstract：Objective To investigate the clinical characteristics of drug-induced liver injury(DILI)caused by omeprazole and to analyze the potential damage mechanisms so as to provide reference for clinical safe medication.Methods Case reports on omeprazole-induced DILI were searched from CNKI,Wanfang Data Knowledge Service Platform,PubMed and other databases.The data were screened and extracted,and the clinical characteristics were analyzed.The potential drug targets of omeprazole were predicted by the SwissTargetPrediction database,and the disease targets of DILI were obtained by the GeneCards database.The inter-section of drug targets and disease targets was further obtained.The protein-protein interaction(PPI)network was constructed using the STRING database,and the PPI network was visually analyzed by the Cytoscape software to screen the core action targets.Gene ontological(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment were performed using the DAVID database.The binding energy of key target protein and omeprazole was verified by molecular docking technique.Results A total of 14 clinical studies were obtained,involving 16 patients,8 males and 8 females,aged between 15 and 85 years old,with an average age of(50.56±18.43)years old.DILI occurred mostly within 20 days after administration.The main type of liver injury was hepatocellular injury.After intervention,14 cases were improved and 2 cases died.A total of 94 common targets of omeprazole and DILI were obtained.The 10 core targets,i.e.CASP3,EGFR,PPARG,CCND1,MAPK3,GSK3B,PARP1,MMP9,PIK3CA and MAPK1 were obtained.The enrichment analysis of the targets showed that omeprazole might mediate DILI mainly through apoptosis,PI3K-Akt and other pathways.Molecular docking showed that omeprazole had a good binding force with the core targets.Conclusion Ome-prazole can cause DILI,and even death in severe cases.The mechanism may induce DILI by regulating apoptosis,PI3K-Akt and other pathways.It is necessary for hospitals to attach great importance to the safety monitoring of use of drugs.