Metabolic changes from exposure to harmful Maillard reaction products and high-fat diet on Sprague-Dawley rats

Rats were fed a high-fat diet and treated with acrylamide (21 mg/kg BW), harmane (7 mg/kg BW), N^Ɛ-(carboxymethyl)lysine (CML; 10 mg/kg BW), or the co-accumulation of the three chemicals to investigate the effects of harmful Maillard reaction products (MRPs) generated by heat processing of potatoes. Damage to the liver, kidney, gastrocnemius, and nervous system was confirmed by serum biochemical testing and histopathology examination after six weeks of feeding. Serum metabolomic analysis was performed using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS). The metabolites detected by GC-TOF-MS were processed using chemometric techniques, and the results were evaluated using a t-test (p < 0.05) and calculated variable importance in projection (VIP) value (>1.5). Significant changes (increase or decrease) were identified in 13 metabolites, compared with the control. These metabolites were gluconolactone, tyrosol, 5-hydroxytryptophan, erythrose 4-phosphate, quinolinic acid, 2-ketobutyric acid, tyrosine, 3-hydroxy-3-methylglutaric acid, desaminotyrosine, L-cysteine, ribonic acid, cysteamine, and tryptophan. Among these, cysteamine and tryptophan are metabolites unique to the co-accumulation of all three test compounds in the treated rats. This study demonstrates that these harmful MRPs exert toxic effects on the liver, kidney, and nervous system via different metabolic pathways. Moreover, co-accumulation of these harmful MRPs caused differing toxic effects and changes in a variety of metabolites. These changes may contribute to the interaction of those harmful MRPs and also affect toxicity at the metabolic level.