Time-resolved lipidomic profiling reveals alterations following 3-MCPDEs exposure in Sprague-Dawley rats.

Lipidomic alterations were investigated in the plasma, liver, kidneys, and testes of Sprague-Dawley (SD) rats at 2, 6, 12, 24, and 48 h after oral administration of 3-MCPDEs (500 mg/kg BW). PLS-DA revealed a clear distinction between the 2 h plasma samples and controls, whereas the largest deviations in organs were observed at 12 h and 24 h post-exposure. Differential lipid analysis in plasma identified 62 putative discriminant lipids, including 34 glycerophospholipids, 13 glycerides, 5 sphingolipids, and 10 other lipid species. Pathway analysis further indicated that glycerophospholipid and sphingolipid metabolic pathways were significantly perturbed following 3-MCPDE exposure. In plasma, glycerophospholipid metabolism was predominantly affected, characterized by marked elevations of lysophospholipids and disrupted homeostasis of PC, PS, and PE species. In contrast, organs exhibited organ-dependent disturbances in sphingolipid metabolism, suggesting tissue-specific vulnerability that may be closely linked to 3-MCPDE-associated toxicity. Overall, these time-resolved lipidomic profiles delineate distinct systemic versus tissue lipid perturbation patterns after 3-MCPDE exposure and provide mechanistic clues for understanding its metabolic toxicity.