This study aimed to investigate the nephrotoxicity in rats administered with chronic low‐dose cadmium (Cd) by ultra‐performance liquid chromatography‐mass spectrometry. A total of 40 male Sprague‐Dawley rats were randomly assigned to four groups, namely: control; low‐dose (0.13 mg/kg·body weight [bw]); middle‐dose (0.80 mg/kg·bw); and high‐dose (4.89 mg/kg·bw). The rats received CdCl2 daily via drinking water for 24 weeks. Rat kidneys were collected for metabonomics analysis. Principal components analysis and partial least‐squares discriminant analysis were used to investigate the metabonomics profile changes in the kidney samples and to screen the potential biomarkers. Ten metabolites were identified in the positive and negative ion modes. Compared with the control group, the intensities of tetranor 12‐HETE, uric acid, hypoxanthine, phenylacetylglycine, guanidinosuccinic acid and xanthosine significantly increased (P < 0.01), and those of imidazolelactic acid, lactose 6‐phosphate, l‐urobilinogen and arachidonic acid significantly decreased (P < 0.01) in the high‐dose group. Results showed that exposure to Cd in rats induced oxidative stress to the kidneys and disrupted amino acid metabolism, fatty acid metabolism and energy metabolism.
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