Mao_2026_Ecotoxicol.Environ.Saf_321_120409

BACKGROUND: T-2 toxin, a highly toxic trichothecene mycotoxin contaminating cereal grains, poses serious health threats. However, its specific effects on hepatic drug-metabolizing enzymes (DMEs) remain poorly characterized. This study aimed to investigate the impact of T-2 toxin on key cytochrome P450 (CYP) and carboxylesterase (CES) enzymes in mouse liver. METHODS: Male C57BL/6 mice were randomly divided into control and T-2 toxin-treated groups, receiving either normal saline or T-2 toxin (0.2 mg/kg) by oral gavage daily for four weeks. Histopathological and ultrastructural alterations were assessed by hematoxylin and eosin staining and transmission electron microscopy. The activity, mRNA, and protein levels of target enzymes in liver tissues or AML12 cells were determined via enzymatic assays, quantitative real-time PCR (qRT-PCR), and western blotting. Transcriptomic profiling (RNA-seq) was performed to identify differentially expressed genes (DEGs) and enriched pathways. RESULTS: T-2 toxin exposure induced hepatocellular injury, including focal necrosis and mitochondrial damage. It significantly altered the activity and expression of multiple phase I DMEs, notably CYP1A2, CYP2B10, CYP3A11, and CES isoforms, at both transcriptional and protein levels. Transcriptomic analysis identified 277 DEGs, predominantly enriched in xenobiotic and drug metabolism pathways, including drug metabolism-cytochrome P450 and xenobiotic metabolic process. CONCLUSION: T-2 toxin induces hepatotoxicity and concurrently alters the expression and activity of key hepatic DMEs. These findings provide insight into T-2 toxin-induced disturbances in xenobiotic metabolism and may contribute to future studies on metabolic biomarkers and toxicological mechanisms.