Advances in targeted treatment of ferroptosis in diabetic kidney disease with SGLT2 inhibitors
Abstract
Ferroptosis, an iron-dependent form of cell death, has recently gained attention in the file of diabetic kidney disease (DKD). It is characterized by the iron-catalyzed lipid peroxide accumulations, distinguishing it from the traditional forms of cell death, such as apoptosis and necrosis. Ferroptosis, which is closely associated with oxidative stress, may contribute to the progression of DKD. The discovery of ferroptosis provides new insights into DKD pathogenesis and may represent a novel therapeutic target. Recent research has shown that Sodium - glucose cotransporter 2 inhibitors (SGLT2i) may exert their kidney protecting effects by modulating ferroptosis-related pathways, thereby indirectly influencing the occurrence of ferroptosis. Therefore, this review systematically elucidates the molecular mechanisms by which SGLT2i target and inhibit ferroptosis in DKD. These mechanisms primarily involve: stabilizing the expression of SLC7A11 and SLC40A1 to restore glutathione synthesis and iron metabolic homeostasis; activating the AMPK/NRF2 axis to enhance antioxidant defense capacity; modulating the BHB-CaMKK2 axis to alleviate mitochondrial oxidative stress and lipid peroxidation via enhanced ketogenesis; down-regulating the HIF-1α/HO-1 pathway to mitigate oxidative injury associated with iron overload; and inhibiting the TGF-β/Smad signaling pathway to attenuate ferroptosis in renal tubular epithelial cells and renal fibrosis. Furthermore, SGLT2i may also indirectly modulate…
Read the paper
Related studies
- Strategy for Mitigating DKA Risk in Patients with Type 1 Diabetes on Adjunctive Treatment with SGLT Inhibitors: A STICH Protocol
- Glucoraphanin: a broccoli sprout extract that ameliorates obesity-induced inflammation and insulin resistance
- SGLT2 Inhibitors in Heart Failure: Targeted Metabolomics and Energetic Metabolism
- Mechanisms of blood pressure reduction with sodium-glucose co-transporter 2 (SGLT2) inhibitors
- Sodium-glucose cotransporter inhibitors: beyond glycaemic control
- Decoding the effects of SGLT2 inhibitors on cardiac arrhythmias in heart failure
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.