Low-molecular-weight fucoidan ameliorates ferroptosis in diabetic kidney disease through SLC7A11/GSH/GPX4 activation

作者：Xiaoxue Chen, Bin Niu, Zifan Zhang, Bo Zhang, Tao Xue, Yanjuan Liu, Zhen Wang, Xinpeng Li · 发表于：Fitoterapia · 年份：2025 · DOI：10.1016/j.fitote.2025.106779 · 被引用次数：7 · 研究领域：Ferroptosis and cancer prognosis、Seaweed-derived Bioactive Compounds、Pregnancy and preeclampsia studies

Ferroptosis plays a crucial role in the development of diabetic kidney disease (DKD), and it is closely associated with oxidative stress. Low-molecular-weight fucoidan (LMWF) has been shown to exert an inhibitory action on oxidative stress. Herein, we investigated whether using LMWF to treat DKD is associated with ferroptosis and evaluated the action of LMWF on DKD using both in vivo and in vitro models. The in vivo DKD model was established by administering a high-glucose and high-fat diet combined with streptozotocin, and H&E and Masson staining were used to observe pathological changes in the kidney and collagen deposition. We assessed GSH, GSSG, and MDA to evaluate oxidative stress and utilized metabolomics to explore potential pathways of action. Prussian blue staining, analysis of 4-HNE and LPO, and PCR array for ferroptosis detection were adopted to observe renal ferroptosis. Our results indicated that LMWF inhibited the progression of DKD while reducing MDA content and increasing GSH content, and metabolomic analysis showed that ferroptosis was the potential mechanism responsible for the effect. Prussian blue staining and 4-HNE, LPO, and PCR assays further confirmed this conclusion. We constructed an in vitro model of HK-2 cells treated with high glucose and intervened with LMWF; this demonstrated that LMWF achieved therapeutic effects in vitro, as LMWF reduced ROS expression and inhibited apoptosis. To investigate the mechanism of action of LMWF treatment after inter...