The iron overload caused by non-enzymatically glycated transferrin triggers oxidative stress and ferroptosis by regulating the PI3/AKT signaling pathway and the expression of Nrf2 to promote renal damage in diabetes.
Findings identify AGE-Tf-associated iron dysregulation as a potential therapeutic target in diabetic kidney disease and deferoxamine or TBHQ ameliorated oxidative stress, iron dysregulation, and ferroptosis in AGE-Tf-treated podocytes and in the kidneys of diabetic rats receiving the WT-Tf vector.