Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, Harbin, Heilongjiang, China.
J Appl Toxicol. 2019 Mar;39(3):441-450. doi: 10.1002/jat.3735. Epub 2018 Oct 16.
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 CdCl 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.
本研究旨在通过超高效液相色谱-质谱联用技术研究慢性低剂量镉（Cd）给药大鼠的肾毒性。将 40 只雄性 Sprague-Dawley 大鼠随机分为 4 组，分别为：对照组；低剂量（0.13mg/kg·体重[bw]）；中剂量（0.80mg/kg·bw）；高剂量（4.89mg/kg·bw）。大鼠通过饮用水每日接受 CdCl2 处理，共 24 周。收集大鼠肾脏进行代谢组学分析。主成分分析和偏最小二乘判别分析用于研究肾脏样本中的代谢组学谱变化，并筛选潜在的生物标志物。在正离子和负离子模式下共鉴定出 10 种代谢物。与对照组相比，高剂量组四氢 12-HETE、尿酸、次黄嘌呤、苯乙酰甘氨酸、胍基琥珀酸和黄嘌呤核苷的强度显著增加（P<0.01），而 1-咪唑乳酸、乳六磷酸、l-尿胆素原和花生四烯酸的强度显著降低（P<0.01）。结果表明，大鼠暴露于 Cd 会引起肾脏氧化应激，并破坏氨基酸代谢、脂肪酸代谢和能量代谢。
