Food Contaminant Deoxynivalenol Causes Muscle Damage by Inducing Lipid Peroxidation and Ferroptosis

Abstract Deoxynivalenol (DON) is a prevalent food contaminant that has been proposed to exert myotoxicity, but direct experimental validation remains insufficient. In this study, we used pig models and cell lines to investigate DON-induced muscle toxicity. In vivo, DON exposure leads to pathological muscle injury, disrupts energy metabolism, alters fatty acid metabolism, promotes the generation of lipid peroxides, and elevates Fe2+ levels. Cellular assays further confirmed that exposure to DON increases intracellular Fe2+ levels, inhibits the glutathione antioxidant pathway, and promotes lipid remodeling, ultimately facilitating lipid peroxidation and triggering ferroptosis. Cellular supplementation with complex lipids and free fatty acids improved C2C12 cell viability, which may be achieved by maintaining membrane lipid homeostasis. Collectively, this study demonstrates that DON induces muscle damage associated with lipid peroxidation and ferroptosis, which may offer a promising direction for the development of protective intervention strategies.