Metabolomic analysis of the toxic effect of chronic exposure of cadmium on rat urine

Abstract

This study aimed to assess the toxic effect of chronic exposure to cadmium through a metabolomic approach based on ultra-performance liquid chromatography/mass spectrometry (UPLC–MS). Forty male Sprague–Dawley rats were randomly assigned to the following groups: control, low-dose cadmium chloride (CdCl₂) (0.13 mg/kg body weight (bw)), middle-dose CdCl₂ (0.8/kg bw), and high-dose CdCl₂ (4.9 mg/kg bw). The rats continuously received CdCl₂ via drinking water for 24 weeks. Rat urine samples were then collected at different time points to establish the metabolomic profiles. Multiple statistical analyses with principal component analysis and partial least squares–discriminant analysis were used to investigate the metabolomic profile changes in the urine samples and screen for potential biomarkers. Thirteen metabolites were identified from the metabolomic profiles of rat urine after treatment. Compared with the control group, the treated groups showed significantly increased intensities of phenylacetylglycine, guanidinosuccinic acid, 4-pyridoxic acid, 4-aminohippuric acid, 4-guanidinobutanoic acid, allantoic acid, dopamine, LysoPC(18:2(9Z,12Z)), and L-urobilinogen. By contrast, the intensities of creatinine, L-carnitine, taurine, and pantothenic acid in the treated groups were significantly decreased. These results indicated that Cd disrupts energy and lipid metabolism. Meanwhile, Cd causes liver and kidney damage via induction of oxidative stress; serum biochemical indices (e.g., creatinine and urea nitrogen) also support the aforementioned results.