Ferroptosis is a non-traditional form of regulated cell death, characterized by
iron overload and lipid peroxidation. Exploration of ferroptosis in
chronic kidney disease (CKD) has been extremely limited to date. In this study, we established a rat model of CKD by 5/6
nephrectomy, treated CKD rats with the ferroptosis inducer,
cisplatin (CDDP), and the ferroptosis inhibitor,
deferoxamine mesylate (DFO), and observed the resulting pathologic changes (injury markers and
fibrosis) and ferroptotic biochemical indices. Kidney
iron deposition, lipid peroxidation,
mitochondrial defects, ferroptosis marker induction, and TUNEL staining positivity were detected in CKD group rats. Further, treatment with CDDP or DFO influenced renal injury and
fibrosis by affecting ferroptosis, rather than apoptosis, and ferroptosis occurs in the remnant kidney due to disordered
iron metabolism. In conclusion, our study shows for the first time that 5/6
nephrectomy induces ferroptosis in the remnant kidney and clarifies the underlying pathogenesis. Moreover, we demonstrate that ferroptosis is involved in CKD progression and represents a therapeutic target in chronic kidney injury and renal
fibrosis.