Health effects of exposure to β-carboline heterocyclic amines: insight into metabolic perturbations and biochemical analysis

Abstract

As a class of bioactive and toxic compounds widely present in foodstuffs, the health effects of dietary exposure to β-carboline heterocyclic amines (HAs) have not been elucidated. Based on our previous research that a typical β-carboline HA (harmane) affects blood glucose metabolism and organ dysfunction, the present study mainly focused on the health effects of dietary exposure to harmane in diabetic Goto-Kakizaki (GK) rats. Twenty-four GK rats were administered daily with harmane (0.1 mg per kg body weight) for eight weeks. A comprehensive evaluation of the health effects of harmane was conducted on serum biochemistry, histopathology, and GC-TOF-MS-based metabolomics. The results showed that harmane exerts non-significant effects on the blood glucose metabolism of GK rats. However, it did cause pathological damage to gastrocnemius nerves and showed adverse effects on brain neurons by significantly activating astrocytes and downregulating brain-derived neurotrophic factor (BDNF), which are potential mechanisms related to the disruption of the normal glutamine–glutamate/γ-aminobutyric acid cycle. Moreover, an increased value of AST and urea, alterations in the amino acid, carbohydrate, purine, pyrimidine, and gut microbiota metabolism as well as the tricarboxylic acid (TCA) cycle could be associated with kidney, liver, and gut dysfunction. Our results suggest that given the role of harmane in nerve injury in GK rats, reducing the production and consumption of β-carboline heterocyclic amines in our daily diets should be considered.