Mitochondrial damage and associated combined toxicity induced by deoxynivalenol and Alternaria toxins co-exposure

Deoxynivalenol and Alternaria toxins are common food contaminants posing significant threats to human and animal health. Although their individual toxicities have been extensively studied, the combined effects of co- exposure remain largely unexplored. Our findings revealed combined toxins displayed concentration- dependent synergistic and antagonistic interactions on human hepatocellular carcinoma cells. Co-exposure significantly reduced mitochondrial activity, increased intracellular ROS levels, and activated the mitochondrial-dependent caspase signaling pathway, ultimately leading to enhanced apoptosis. Metabolomics analysis revealed that combined exposure severely disrupted multiple key metabolic processes, including those related to energy (NAD+, adenosine, AMP, and ADP), amino acids (L-aspartate, l-glutamate), and carbohydrate (Glucose-6-phosphate) metabolisms. These findings highlight that co-occurrence exacerbates the disruption of overall metabolic balance, potentially impairing the normal function of cells by affecting energy production, protein synthesis, and cell proliferation. This study underscores the importance of considering combined mycotoxin exposure and provided possible ideas for inhibiting or mitigating toxicity to ensure food safety.