The Protective Effects of Lycopene Against T2 Mycotoxin-Induced Apoptosis in Mouse Liver and Its Transcriptional Mechanisms

Background: T-2 toxin, a highly toxic Fusarium-derived mycotoxin, frequently contaminates feed and poses significant risks to livestock production and food safety by inducing severe apoptotic damage in the liver, which is the primary organ responsible for toxin metabolism and detoxification. Lycopene, a natural carotenoid antioxidant, exhibits possible hepatoprotective effects against various exogenous toxins; however, there are currently few studies that analyze, from a transcriptomic perspective, how lycopene mitigates T-2 toxin-induced apoptosis in liver tissue. Methods: mouse model of T-2 toxin exposure was established, with low- and high-dose lycopene co-administered for 5 weeks. Results: Transcriptomic analysis and TUNEL staining demonstrated that T-2 toxin stimulation induced marked activation of apoptotic-signaling pathways in liver tissue, while lycopene intervention significantly suppressed this transcriptional activation and alleviated T-2 toxin-provoked hepatocyte DNA-fragmentation signals, together with decreased transcription of pro-apoptotic genes. Comprehensive investigation revealed that T-2 toxin upregulated the RORC (RAR related orphan receptor C) and enhanced its occupancy at the promoter regions of apoptosis-related genes (TNFSF10, PMAIP1, IL18, and RNASEL), as verified by ChIP-qPCR assays. Lycopene strongly reversed the T-2 toxin-induced increase in RORC expression and its binding to apoptosis-related gene promoters. Analysis of the protein—protein interaction network further revealed potential molecular links between RORC and multiple core apoptotic pathway components. Conclusions: Lycopene protects mouse liver from T-2 toxin-induced apoptotic injury, while RORC is identified as a potential candidate regulatory factor associated with this protective effect. This study provides experimental evidence at the transcriptomic level for the use of lycopene in the prevention and treatment of liver tissue damage caused by T-2 toxin.