Investigating the potential molecular mechanisms of dibutyltin dilaurate induced brain injury: a network toxicology and molecular docking approach.

Dibutyltin dilaurate (DBTDL) is an organotin compound widely used in industrial chemical generation, recognized for its toxicity upon exposure. However, its association with brain injury remains unexplored. This study aims to identify and validate the molecular targets of DBTDL-induced brain toxicity using network toxicology approach and molecular docking analysis, and to elucidate its mechanisms. We used comprehensive databases including ChEMBL, STITCH, GeneCards and OMIM to screen potential targets related to DBTDL exposure and brain injury. STRING database and Cytoscape software were further analyzed to identify the core targets. Functional and pathway enrichment analyses were conducted to infer biological relevance. Molecular docking was utilized to predict the interactions between DBTDL and its targets. Expression validation and mechanism exploration were performed in vitro using human microglial cell (HMC3) and human brain microvascular endothelial cells (HBMEC). We identified 143 potential target and 24 core targets related to DBTDL exposure and brain injury. The core targets were mainly enriched in signal transduction, synaptic, hormonal and inflammatory pathways. Molecular docking revealed high-affinity interactions between DBTDL and five core targets, demonstrating binding energies of -7.8 (AGT), -9.9 (AGTR1), -11.2 (GNB1), -6.7 (GNG2) and -3.7 (POMC). In vitro validation was conducted using HMC3 and HBMEC cells. These cells were exposed to concentrations ranging from 0.1 to 20 μM, which are reported to be biologically effective. The results revealed that DBTDL exhibits significant cytotoxicity on two types of cells. Additionally, DBTDL activates oxidative stress pathways by inducing intracellular ROS production. After DBTDL treatment, the expressions of all five core targets were significantly upregulated, and expressions of neurotrophic factors were also increased. Our results identified a set of core targets for DBTDL-induced brain injury and indicate that DBTDL may affect neuroinflammatory and neurotoxicity in the brain through these targets. Our results not only advance our knowledge of DBTDL-induced brain injury and potential therapeutic interventions, but also emphasize the need for regulatory measures to limit DBTDL exposure and protect public health.