Ferroptosis in Mycotoxin-Induced Toxicity: Molecular Mechanisms, Intervention Implications, and Future Directions

Chronic exposure to mycotoxin-contaminated food and feed induces systemic toxicity in humans and animals, with emerging evidence identifying ferroptosis as a key mechanism driving this pathology. Key mycotoxins, including deoxynivalenol, aflatoxin B1, T-2 toxin, fumonisin B1, zearalenone, ochratoxin A, and patulin, trigger ferroptosis through interconnected pathways: iron metabolism disruption, lipid peroxides accumulation, Glutathione Peroxidase 4 (GPX4) antioxidant system imbalance, Ferroptosis Suppressor Protein 1 (FSP1) pathway modulation, and mitochondrial homeostasis disruption. This review systematically elucidates the role of ferroptosis in mycotoxin-induced organ-specific and systemic toxicity, dissecting its regulatory networks, from molecular targets to signaling cascades. Importantly, ferroptosis represents a key pathway for controlling mycotoxin toxicity, with interventions extending beyond synthetic inhibitors to include natural compounds (e.g., polyphenols), selenium, prebiotics, melatonin, and L-fucose. These agents counteract mycotoxins-driven ferroptosis via antioxidant reinforcement, iron chelation, and lipid metabolism modulation, underscoring their translational potential. By addressing current research gaps and proposing future research directions, this work advances a ferroptosis-centric framework for safeguarding the health of livestock, poultry, and humans.