Transcriptomic analysis suggests ferroptosis as a potential mechanism of fipronil-induced cytotoxicity in human glioblastoma cells.

Fipronil (FPN), a widely used phenylpyrazole insecticide, has been associated with neurotoxicity. However, the precise molecular mechanisms underlying its effects on human neural cells, particularly glioblastoma, remain poorly understood. This study aimed to investigate the cytotoxic effects and molecular mechanisms of FPN on the human glioblastoma cell line GBM 8401. GBM 8401 cells were treated with FPN (0-200 μM) for 24 and 48 h. Cell viability was assessed using CCK-8 assay. Transcriptomic changes were analyzed using RNA sequencing. Differentially expressed genes (DEGs) were identified, and gene enrichment analysis was performed using KEGG, Gene Ontology (GO), and Disease Ontology databases. FPN significantly reduced cell viability in a concentration- and time-dependent manner. Transcriptome analysis identified 3381 DEGs at 24 h and 2644 DEGs at 48 h, revealing extensive gene expression changes. A core set of 1444 genes was consistently differentially expressed at both time points, representing the most robust transcriptomic response to FPN treatment. Functional enrichment analysis of commonly regulated DEGs showed significant enrichment in the ferroptosis pathway, alongside the p53 signaling pathway. Pathways related to the cell cycle, DNA replication, and DNA repair were primarily down-regulated. This study's transcriptomic evidence is consistent with FPN inducing cytotoxicity in human glioblastoma cells partly through the potential activation of the ferroptosis pathway, while suppressing cell cycle and DNA repair mechanisms.