Overview of Ferroptosis in Cadmium Toxicity

Cadmium (Cd), a ubiquitous heavy metal pollutant with significant environmental persistence and bioaccumulative potential, poses a severe threat to human health and ecological safety. As a widely recognized endocrine disruptor, Cd has attracted sustained research attention in environmental and public health domains due to its multifaceted toxicity. Recent advances in regulated cell death mechanisms have revealed ferroptosis is a distinct form of cell death (apoptosis, autophagy, necroptosis, and pyroptosis) characterized by iron overload and lipid peroxidation. A novel insight highlighted in this review is the direct linkage between Cd toxicity and ferroptosis, which provides a new perspective for understanding the toxic mechanism of Cd. This review systematically synthesizes emerging evidences on Cd-induced ferroptosis. Cd triggers ferroptosis by impairing mitochondrial structure and function, disrupting iron metabolism, promoting lipid peroxidation, and suppressing antioxidant systems. Notably, therapeutic interventions using selenium and melatonin have protective effect on Cd-induced ferroptosis by modulating iron metabolism, enhancing ROS scavenging capacity, and restoring redox balance. Future research priorities should focus on elucidating key molecular events in Cd-induced iron dysregulation. This review underscores the translational potential of targeting ferroptosis in Cd toxicity mitigation strategies, offering a mechanistic framework for environmental intervention and therapeutic innovation.