Lycopene Alleviates T-2 Toxin-Induced Liver Inflammatory Injury Associated with Attenuated NLRP3 Inflammasome Activation

Abstract T-2 toxin (T-2) is a potent mycotoxin that causes liver injury, but its underlying mechanisms and effective nutritional interventions remain incompletely understood. Although NLRP3 inflammasome activation has been implicated in T-2 toxin-induced hepatotoxicity, its precise role and regulation remain unclear. Here, wild-type and Nlrp3-deficient mice were used to investigate the role of the NLRP3 inflammasome in T-2-induced hepatotoxicity and the protective effects of lycopene (LYC). T-2 exposure induced hepatic dysfunction, histopathological injury, inflammatory cytokine production, and NLRP3 inflammasome activation, whereas Nlrp3 deficiency markedly alleviated these alterations. Mechanistically, T-2 reduced AMPK/SIRT1/PGC-1α/FXR signaling, which was associated with NLRP3 inflammasome activation. LYC supplementation restored AMPK/SIRT1/PGC-1α/FXR signaling, suppressed NLRP3 inflammasome activation and downstream inflammatory responses, and alleviated liver injury. These findings suggest that suppression of the AMPK/SIRT1/PGC-1α/FXR pathway may contribute to T-2-induced NLRP3 inflammasome activation and support further investigation of LYC as a nutritional strategy against mycotoxin-induced liver injury.