Fucoidan Ameliorates Contrast-Induced Acute Kidney Injury in Mice by Modulating the TLR4/NF-κB and Nrf2/GPX4 Pathways

Objectives: The purpose of this study was to investigate the protective effects and underlying mechanisms of fucoidan on contrast-induced acute kidney injury (CI-AKI) in mice, focusing on the TLR4/NF-κB and Nrf2/GPX4 pathways. Methods: Five-week-old male ICR mice were randomly divided into normal control, contrast model, low-dose (100 mg/kg), and high-dose (300 mg/kg) fucoidan groups. Renal index, biochemical markers, histopathology, oxidative stress indicators, inflammatory cytokine levels, and the expression of TLR4/NF-κB, Nrf2/HO-1, and ferroptosis-related proteins were assessed. Untargeted metabolomics followed by KEGG pathway enrichment was also performed. Results: Our results showed that contrast successfully established the CI-AKI model, as evidenced by an increased kidney index, abnormal biochemical parameters, severe renal pathological damage, oxidative stress imbalance, inflammatory activation, ferroptosis, and metabolic disturbances. Fucoidan dose-dependently improved kidney index and biochemical markers, alleviated pathological injury, enhanced antioxidant capacity, suppressed inflammation and ferroptosis, and reversed metabolic pathway disorders (e.g., purine and glycerophospholipid metabolism), with the high dose showing more pronounced effects. Conclusions: Fucoidan could effectively ameliorate CI-AKI, and its effects are closely associated with the inhibition of the TLR4/NF-κB pathway, activation of the Nrf2/HO-1 pathway, regulation of ferroptosis-related proteins, and improvement of key metabolic disturbances, suggesting a new research direction for the prevention of CI-AKI.