Cadmium Induces Kidney Damage by Regulating Ferroptosis

Cadmium (Cd) is a toxic heavy metal that accumulates in organisms and threatens health via the food chain. The kidney is a key target organ for Cd toxicity. Ferroptosis, a novel form of cell death distinct from apoptosis, necrosis, and autophagy, may be involved in Cd-induced kidney injury. Our study used in vivo and in vitro models to explore this link. Cd exposure caused pathological changes and increased Cd levels in pig kidneys, along with significant alterations in oxidative stress markers (ROS, MDA, LPO) and ferroptosis. In vitro, CdCl₂ exposure induced changes in mRNA and protein levels of oxidative stress and ferroptosis-related genes in PK-15 cells, increased intracellular iron, and decreased ATP. However, these effects were blocked by Nrf2 inhibitors (ML385). Our results suggested that Cd induced ferroptosis in renal cells via the Keap1-Nrf2-HO-1 pathway, revealing a new mechanism of Cd nephrotoxicity.