Fig. 8

The schematic diagram illustrates the involvement of ferroptosis in the kidneys of db/db mice. HG has been found to induce renal fibrosis and ferroptosis in diabetic mice. This is attributed to the increased levels of TfR1 and DMT1, as well as the decreased level of FPN1, which results in elevated LIP in the kidney. The excess of labile iron pool (LIP), primarily consisting of Fe²⁺, exacerbates the generation of lipid ROS in response to the Fenton reaction. Furthermore, the reduced expression of Fsp1 hinders the CoQ10 to its reduced form, CoQ10(H₂), thereby impeding its antioxidant effects. Additionally, the imbalance in the Xc⁻ system disrupts the exchange and synthesis of GSH, leading to the inhibition of GSH-dependent antioxidant defences and ultimately resulting in ferroptosis. Liraglutide has the potential to enhance the expression of Fsp1 and ameliorate the Xc⁻ system, thereby mitigating the ferroptosis response in the renal tissue of db/db mice.