Insights from Metabolomic and Transcriptomic Analyses into Sulforaphane’s Protective Mechanism Against Deoxynivalenol Toxicity via Spermine Regulation

Deoxynivalenol (DON) is a mycotoxin ubiquitously present in the environment. Emerging evidence demonstrated that sulforaphane (SFN) exerts potent protective effects against DON-triggered cytotoxicity through multimodal mechanisms. This study aimed to investigate the protective mechanism of SFN during DON exposure. Untargeted metabolomics of IPEC-J2 cells revealed a total of 399 differential metabolites between the DON and control group and 365 differential metabolites between the SFN + DON and DON group. KEGG enrichment was performed to investigate the potential regulatory pathways. The transcriptome identified a total of 1839 differential expression genes (DEGs) between DON and SFN + DON groups. This result indicated that DON exposure and SFN treatment have a profound impact on cellular metabolism and genes. Integrated analysis of the transcriptome and metabolome showed that spermine was a potential biomarker for SFN treatment. SFN increased spermine abundance by regulating genes in glutathione, beta-alanine, and arginine and proline metabolism pathways. Functional experiments demonstrated that spermine alleviated DON-induced oxidative stress, as evidenced by increased cell viability, reduced ROS levels, restored mitochondrial membrane potential (ΔΨm), and normalized antioxidant enzyme activity. Moreover, spermine significantly decreased the cell apoptosis rate induced by DON, which suggested that spermine significantly alleviated the DON-induced cytotoxicity. Overall, these findings elucidated the protective role of SFN through spermine-related mechanisms against the toxicity of DON.