Fucoidan Attenuates Lead-Induced Liver Injury Associated with IGFBP1 and Gut Microbiota-Derived Tryptophol Metabolism

Lead (Pb) exposure induces liver injury through oxidative stress, inflammation, and gut–liver axis disruption. This study evaluated the protective effects and associated mechanisms of fucoidan (FU) against Pb-induced liver injury in mice. C57BL/6 mice were exposed to lead acetate and treated with FU. High-dose FU (FU-H) improved food intake, body weight, and liver index; decreased Pb levels in serum and liver; and increased fecal Pb content. Compared with the Model group, FU-H reduced serum ALT, AST, and ALP by 54.8%, 38.6%, and 21.7%, respectively. FU-H restored hepatic SOD and GSH by 10.9% and 46.5% and decreased hepatic MDA by 45.9%; it also restored serum SOD and GSH by 30.4% and 24.0%, decreased serum MDA by 19.6%, and suppressed TNF-α, IL-6, and IL-1β by 15.7%, 21.1%, and 14.9%, respectively. Integrated RNA sequencing and network toxicology suggested that insulin-like growth factor-binding protein 1 (IGFBP1) may be associated with FU-mediated protection, and recombinant IGFBP1 partly weakened FU-associated hepatoprotection. Moreover, 16S rRNA sequencing and untargeted metabolomics showed that FU reshaped Pb-disrupted gut microbiota and altered fecal tryptophan metabolism. Exogenous tryptophol supplementation partially alleviated Pb-induced liver injury. Overall, FU protection was associated with reduced Pb burden, IGFBP1-related redox modulation, and gut microbiota-derived tryptophol metabolism.