Eicosapentaenoic Acid Modulates 3-Chloro-1,2-propanediol Dipalmitate Ester-Induced Disrupted Metabolism: A Dual-Approach Analysis Using Nontargeted Metabolomics and Computational Modeling

3-Chloropropane-1,2-diol (3-MCPD) and its esters (3-MCPDE) are common food contaminants with toxic effects. Our study examined how 3-MCPDE exposure affects metabolism and the potential protective roles of eicosapentaenoic acid (EPA) using urine metabolomics and molecular docking. Short-term exposure to 3-MCPDE and 3-MCPD affected similar metabolic pathways. While EPA alone caused few metabolic changes, it produced significant metabolic alterations when combined with 3-MCPDE exposure. EPA demonstrated modulation of 3-MCPDE-induced metabolic disruptions, including alanine, aspartate, and glutamate metabolism and arginine and proline metabolism. Molecular docking analysis revealed that 3-MCPD and EPA exhibited better binding affinity to alanine aminotransferase 2 than the original ligand, potentially explaining the l-alanine accumulation. Virtual screening identified key structural characteristics for optimal protein binding, including balanced hydrophobic interactions and hydrogen-bonding networks. This study shows insights into EPA's health benefits against 3-MCPDE-induced toxicity and a framework for developing nutritional interventions.