Lycopene Alleviates T-2 Toxin-Induced Liver Inflammatory Injury Associated with Attenuated NLRP3 Inflammasome Activation
Xu Yang, Haodong Wang, Bo Wang, Wenxi Song, Zhihui Zhang, Shanshan Zhang, Yuliang Xia, Zhenhao Ma, Yanfei Li, Xuebing Wang, Cong ZhangAbstract
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.