Metabolic perturbations and health impact from exposure to a combination of multiple harmful Maillard reaction products on Sprague-Dawley rats

Abstract

The present study aimed to investigate the metabolic perturbations and health impact of the co-accumulation of Maillard reaction products (MRPs), including acrylamide, harmane, and N^ε-(carboxymethyl)lysine (CML), via serum biochemical and histopathological examinations as well as metabolomic analysis. Sprague-Dawley rats were treated with acrylamide (2 mg per kg body weight [bw]), harmane (1 mg per kg bw), CML (2 mg per kg bw), and combinations of these MRPs. Harmane did not cause adverse effects on the health of rats, whereas acrylamide and CML resulted in significantly (P < 0.05) decreased insulin sensitivity (HOMA-IR > 1), increased oxidative stress levels, and pathological injuries to the pancreas, liver, and gastrocnemius. Owing to the antioxidant and anti-diabetic activities of harmane, the effects of the combination of the MRPs on oxidative stress levels, blood glucose metabolism, and pathological injuries to the pancreas and gastrocnemius were relieved. However, new health problems, including pathological injury of the kidneys and increased cancer risk, were observed. Metabolomic analysis revealed that this may be related to the effects of MRPs on the arginine biosynthesis pathway, which resulted in the abnormal metabolism of fumaric acid and the tricarboxylic acid cycle. These results indicated that the mechanisms of the combined effect of MRPs and their effects on health cannot be predicted from the effects of individual MRPs.