Interaction of deoxynivalenol and copper: Cellular and molecular insights in mouse liver cells

Deoxynivalenol (DON) and copper (Cu) are crucial food-related contaminants associated with health risks in both animals and humans. This study investigated the individual and combined effects of DON and Cu on a mouse hepatocyte line NCTC1469 cells. The results demonstrated that both DON and Cu induced ultrastructural damage, promoted mitochondrial vacuolization, increased pro-inflammatory cytokine levels, such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha, reduced cell viability, and suppressed antioxidant enzyme activity, including glutathione and superoxide dismutase. Notably, DON + Cu enhanced cell viability compared to DON alone. In addition, co-treatment significantly reduced IL-1β levels relative to DON alone at 0.625, 1.25, and 2.5 μM. Transcriptome sequencing revealed that both DON alone and DON-Cu co-exposure triggered numerous differentially expressed genes, which were notably enriched in autophagy related pathways, such as ribosome biogenesis in eukaryotes, lysosome, spliceosome, and cell cycle. Meanwhile, the relative protein ratio of LC3-II/LC3-I was elevated at 0.65 μM DON, while the p62 expression was decreased in a dose-dependent manner compared to the control. In summary, DON exerts toxic effects on mouse hepatocytes, while Cu can mitigate DON-induced cellular damage at low concentrations, likely through involvement in Beclin-1/p62 related autophagic regulation.