Fucoxanthin Ameliorates Kidney Injury by CCl4-Induced via Inhibiting Oxidative Stress, Suppressing Ferroptosis, and Modulating Gut Microbiota

Chemical-induced kidney injury represents a substantial health risk, with ferroptosis, a type of cell death caused by lipid peroxidation, playing a role in numerous kidney ailments. Fucoxanthin (Fx), a natural carotenoid known for its antioxidant capabilities, has shown promise in alleviating renal injury, but its exact mechanisms are yet to be fully understood. Carbon tetrachloride (CCl₄) is recognized as a powerful nephrotoxic substance, and this study explores the therapeutic effects of Fx on oxidative stress, ferroptosis and intestinal microbiota in mouse kidneys subjected to CCl₄ exposure. The mice were randomly assigned to control, model, colchicine groups (0.1 mg/kg/d), and Fx (50, 100 mg/kg/d) group and underwent related treatments for 4 weeks. Then, we evaluated their renal function, histological alterations in the kidneys, colon, and jejunum, and the levels of related proteins (i.e., Nrf2, GPX4, SLC7A11, HO-1, TFR1, NQO1, GCLM, FTL). Additionally, their gut microbiota was analyzed using 16S rRNA gene sequencing. The results showed that compared to the CCl₄ group, Fx treatment led to lower serum creatinine and blood urea nitrogen levels, reduced malondialdehyde activity in kidneys and intestinal tissues, and increased activity of antioxidant enzymes. Fx also reduced dysbiosis and enhanced the diversity of intestinal flora. In summary, Fx reduced oxidative stress and ferroptosis and partially restored intestinal bacteria, thus improving CCl₄-induced renal damage in mice. These results suggest Fx as a potential therapeutic option for kidney injuries related to oxidative stress. Further research is needed to clarify its precise mechanisms and potential clinical implications.