Short-Term Exposure to 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine Induces Colonic Energy Metabolism Disorders in Rats.

Abstract

2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most abundant heterocyclic aromatic amines generated in thermally processed meat products, and the toxicities of its short-term exposure in the intestines remain unclear. This study aimed to elucidate the short-term PhIP toxicity in colons through administering PhIP orally to rats for 4 weeks. The results indicated that short-term PhIP exposure induced colonic oxidative stress, a significant decrease of serum triglyceride, and a disrupted colonic gene expression pattern associated with mitochondrial electron transport chain and energy metabolism. Thirteen energy metabolites, including lactate and d-erythrose-4-phosphate, showed significant changes under short-term PhIP effects. Energy metabolism pathway analysis revealed that PhIP-induced colonic energy metabolism disorders are characterized by inhibited glycolysis and enhanced tricarboxylic acid cycle. Further investigation found that PhIP altered the energy metabolic phenotype of colon epithelial cells to increase aerobic respiration. In summary, our study provides new insights into the colon toxicity induced by a short-term PhIP exposure.