Integrative network toxicology and computational modeling uncover the mechanism of aflatoxin B1-induced nephrotoxicity.

Aflatoxin B1 (AFB1) is a highly toxic mycotoxin that causes severe renal injury, yet the molecular basis of its nephrotoxicity remains poorly defined. Here, we integrated multi-omics data with computational modeling to elucidate the mechanisms of AFB1-induced kidney damage. Three human renal transplant biopsy microarray datasets (GSE1563, GSE30718, and GSE61739), comprising 121 injury samples and 84 control samples and representing distinct forms of transplant-associated renal injury, including acute rejection and ischemic kidney injury, were analyzed using differential expression and weighted gene co-expression network analyses, which identified 174 injury-related genes. A total of 145 AFB1-associated targets were obtained from multiple public datasets. Intersection analysis between these two gene sets identified RXRB and F11 as core hub genes potentially involved in AFB1-induced renal injury. Immune infiltration and gene set enrichment analyses suggested their involvement in immune regulation and toxicity-related signaling pathways. Molecular docking demonstrated favorable binding of AFB1 to RXRB and F11, with binding energies of -9.9 and -7.4 kcal/mol, respectively, while molecular dynamics simulations further confirmed the stability of these complexes. Together, this integrative multi-omics and modeling approach reveals key molecular determinants of AFB1-induced renal toxicity and offers a theoretical foundation for developing targeted interventions against AFB1-related kidney disorders.