The Evaluation of Toxicity Induced by Psoraleae Fructus in Rats Using Untargeted Metabonomic Method Based on UPLC-Q-TOF/MS.
The Evaluation of Toxicity Induced by Psoraleae Fructus in Rats Using Untargeted Metabonomic Method Based on UPLC-Q-TOF/MS.
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基于UPLC-Q-TOF/MS的非靶向代谢组学方法评价补骨脂对大鼠的毒性
DOI：
10.1155/2017/6207183
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Xu Y;Zhao Y;Xie J;Sheng X;Li Y;Zhang Y
补骨脂果是豆科植物补骨脂的干燥成熟果实，具有温肾益阳、温脾等功效。然而，大剂量可引起肝和肾毒性。因此，有必要对补骨脂的毒性进行系统的评价。虽然传统的生化指标和病理试验已被用于评价药物的安全性，但这些方法缺乏敏感性和特异性，因此迫切需要一种快速灵敏的分析方法。本研究采用超高效液相色谱-四极杆飞行时间质谱法（UPLC-Q-TOF/MS）分析大鼠血浆代谢谱。采用偏最小二乘判别分析（PLS-DA）检测血浆样品中代谢物的变化。与对照组比较，给药7 d后病理切片显示肝肾毒性，代谢趋势发生改变。最后，筛选了13个与补骨脂毒性相关的潜在生物标志物。代谢途径包括甘油磷脂代谢、氨基酸代谢、能量代谢等。这些生物标志物的发现为更好地解释补骨脂的肝毒性和肾毒性奠定了基础，并为补骨脂的安全性评价提供了保障。
Psoraleae Fructus is the dry and mature fruit of leguminous plant Psoralea corylifolia L., with the activity of warming kidney and enhancing yang, warming spleen, and other effects. However, large doses can cause liver and kidney toxicity. Therefore, it is necessary to evaluate the toxicity of Psoraleae Fructus systematically. Although traditional biochemical indicators and pathological tests have been used to evaluate the safety of drug, these methods lack sensitivity and specificity, so a fast and sensitive analytical method is urgently needed. In this study, an ultraperformance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) method was used to analyze the metabolic profiles of rat plasma. The changes of metabolites in plasma samples were detected by partial least squares-discriminant analysis (PLS-DA). Compared with the control group, after 7 days of administration, the pathological sections showed liver and kidney toxicity, and the metabolic trend was changed. Finally, 13 potential biomarkers related to the toxicity of Psoraleae Fructus were screened. The metabolic pathways involved were glycerol phospholipids metabolism, amino acid metabolism, energy metabolism, and so forth. The discovery of these biomarkers laid a foundation for better explaining the hepatotoxicity and nephrotoxicity of Psoraleae Fructus and provided a guarantee for its safety evaluation.
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DOI：
10.1016/j.csbj.2014.08.001
发表时间：
2014-07
影响因子：
6
作者：
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