Biochemical interactions of dietary food contaminants with cytochrome P450 2E1: an in silico approach

Aim: Food contaminants such as acrylamide, 3-monochloropropane-1,2-diol (3-MCPD), glycidyl stearate, deoxynivalenol, hydroxymethylfurfural, and zearalenone represent significant toxicological concerns in humans due to their potential genotoxic, hepatotoxic, and carcinogenic properties. This study aimed to investigate the molecular interactions of these contaminants with cytochrome P450 2E1 (CYP2E1), a key enzyme in xenobiotic metabolism, using an in silico approach. Methods: Molecular docking simulations were performed to assess the binding affinities and interaction profiles of selected food contaminants with the active site of human CYP2E1. The docking scores and binding poses were analyzed to predict possible metabolic outcomes and risks associated with exposure. Results: Docking analysis revealed variable binding affinities among the tested contaminants. Glycidyl stearate, zearalenone, and deoxynivalenol demonstrated stronger binding interactions (higher docking scores) compared to acrylamide and 3-MCPD, suggesting higher potential for CYP2E1-mediated metabolism. Quantitative results have been added: glycidyl stearate, deoxynivalenol, and zearalenone showed the stronger binding energies (−6.4, −7.2, and –7.9 kcal/mol), while acrylamide and 3-MCPD were weaker (−3.7 and −4.1 kcal/mol). Hydroxymethylfurfural showed an intermediate binding affinity (ΔG = –5.3 kcal/mol), suggesting a moderate potential for CYP2E1-mediated metabolism. Differential binding patterns highlighted possible metabolic activation or detoxification pathways. Conclusions: The results indicate that CYP2E1 plays an important role in mediating the biochemical responses to multiple food contaminants. Stronger interactions with certain contaminants suggest a higher risk of metabolic activation, which may contribute to their toxic effects. This study demonstrates the utility of molecular docking for predicting human biochemical responses and supports its use as a complementary tool in food safety risk assessment.