Unraveling the neurotoxic mechanisms of tranexamic acid in epilepsy induction: a network toxicology and molecular docking approach.

Abstract

Tranexamic acid, an antifibrinolytic drug, is effective for surgical hemostasis and bleeding-related disorders but may induce neurotoxicity, such as epilepsy. The mechanisms driving TXA-induced epilepsy remain poorly understood, as traditional toxicology approaches fall short in capturing its complex toxicity profile. This study employs network toxicology and molecular docking to elucidate the multi-target molecular mechanisms of TXA-induced epilepsy, aiming to enhance its safe clinical application. TXA toxicity was predicted using ADMETlab2.0, PROTOX3.0, toxCSM, and ADMET-AI, with SMILES sequences obtained from PubChem, and a TXA target library was constructed using databases such as ChEMBL. EP-related targets were screened from databases such as GeneCards, and target intersections were analyzed using R software. Networks were constructed using Cytoscape and STRING, with GO and KEGG analyses performed to investigate molecular pathways. Molecular docking was conducted using the CB-Dock2 platform to analyze TXA binding to core targets. TXA poses a neurotoxicity risk, with 51 intersecting targets identified between TXA and EP, among which GABRA1, GABBR2, GABRA5, GABRA2, and GAD1 exhibited the greatest relevance. Analysis revealed that TXA induces EP by disrupting GABA signaling and synaptic function. The PPI network confirmed five core targets, and GO and KEGG analyses elucidated their roles in neural suppression. Molecular docking demonstrated stable binding of TXA to these targets, with Vina scores ranging from - 5.2 to - 6.9. This study elucidates the mechanisms of TXA-induced EP through network toxicology and molecular docking, confirming its interference with GABA-related targets and neural suppression functions. The study overcomes the limitations of traditional toxicology, providing a scientific basis for the safe use of TXA and prevention of neurotoxicity.