OBJECTIVE To investigate the mechanism of liver and kidney injury and allergies induced by amphotericin B(AmB) through network pharmacology, cellular experiments, and animal experiments.

METHODS Biochemical indicator analysis was performed on patients administered AmB at Hanzhong Central Hospital. The toxicity of AmB was predicted using the ProTox-Ⅱ platform, while its potential targets were identified through the PharmMapper, CTD, and SwissTargetPrediction databases. Using the DAVID database, potential intervention mechanisms of AmB were analyzed through GO and KEGG pathway enrichment. Simultaneously, target retrieval was performed using the DisGeNET and OMIM databases, followed by an intersection analysis to identify overlapping targets between potential AmB targets and known disease-related targets. The protein-protein interaction(PPI) network of these intersecting targets was constructed using STRING 11.0 and further subjected to network topology analysis with Cytoscape 3.8.0 software. In cellular experiments, LAD2 cells treated with varying concentrations of AmB were analyzed for the levels of β-aminoglucosidase, histamine, TNF-α, MCP-1, and IL-4. Additionally, a mouse model of AmB-induced liver and kidney injury was established. Changes in mouse body weight were recorded, organ indices were calculated from liver and kidney samples, and pathological sections were observed.

RESULTS Clinical data analysis revealed significant alterations in several biochemical markers following AmB administration, indicating its impact on liver and kidney function. Additionally, allergic reactions, including chills and fever, were observed in some patients during initial treatment, suggesting that the underlying mechanism may differ from typical typeⅠ allergic reactions. Network pharmacological analysis further hypothesized that renal injury and allergic reactions might be associated with cellular inflammation and mast cell activation. In vivo and in vitro experiments demonstrated that AmB stimulated LAD2 cells to degranulate and release cytokines, while also causing liver and kidney damage in mice, thereby supporting the hypothesis that AmB might cause liver and kidney toxicity as well as allergic reactions.

CONCLUSION AmB can cause liver and kidney damage, as well as trigger mast cell anaphylactoid reactions.