Cadmium Induces Kidney Damage by Regulating Ferroptosis

Area of Science:

• Toxicology
• Cell Biology
• Environmental Health

Background:

• Cadmium (Cd) is a toxic heavy metal posing health risks through the food chain.
• The kidney is a primary target organ for cadmium toxicity.
• Ferroptosis, a distinct form of cell death, is potentially implicated in cadmium-induced kidney injury.

Purpose of the Study:

• To investigate the role of ferroptosis in cadmium-induced nephrotoxicity.
• To elucidate the molecular mechanisms underlying cadmium's effects on renal cells.

Main Methods:

• In vivo studies using pig kidneys and in vitro experiments with PK-15 cells.
• Assessment of pathological changes, cadmium levels, oxidative stress markers (ROS, MDA, LPO), intracellular iron, and ATP levels.
• Analysis of mRNA and protein expression of ferroptosis-related genes and the Keap1-Nrf2-HO-1 pathway.

Main Results:

• Cadmium exposure led to kidney damage, increased cadmium accumulation, elevated oxidative stress, and ferroptosis markers in vivo.
• In vitro, cadmium chloride induced ferroptosis-like changes, increased intracellular iron, and decreased ATP in renal cells.
• Nrf2 inhibition blocked cadmium-induced ferroptosis, implicating the Keap1-Nrf2-HO-1 pathway.

Conclusions:

• Cadmium induces ferroptosis in renal cells, contributing to nephrotoxicity.
• The Keap1-Nrf2-HO-1 pathway is a key mediator of cadmium-induced ferroptosis.
• This study reveals a novel mechanism of cadmium nephrotoxicity involving ferroptosis.