Network Toxicology and Molecular Docking Analysis of Antituberculosis Drug-Induced Hepatotoxicity

Drug-induced hepatotoxicity (DIH) is a serious adverse effect of Antituberculosis (anti-TB) therapy, frequently causing treatment interruption and poor outcomes. This study combines network toxicology, molecular docking technology, and in vivo experiments to clarify the molecular mechanisms of anti-TB drug-induced hepatotoxicity. We identified key molecular targets and signaling pathways associated with hepatotoxicity by integrating drug-disease intersection-target interactions and pathway enrichment analyses. Molecular docking assessed the binding affinity between Antituberculosis drugs (e.g., isoniazid, rifampicin, pyrazinamide) and hub targets, with in vivo experiments further validating changes in mRNA expression of these core targets. Our findings suggest that NFE2L2, NFKB1, MAP2K1, MAPK14, IGF1R, and GSK3B may represent important targets for antituberculosis drug-induced hepatotoxicity, with oxidative stress, apoptosis, and lipid accumulation potentially serving as underlying mechanisms. These insights deepen our understanding of the molecular basis of anti-TB drug-induced hepatotoxicity and suggest potential targets for developing hepatoprotective strategies during tuberculosis treatment.