Plasma metabonomics study on toxicity biomarker in rats treated with Euphorbia fischeriana based on LC-MS
Plasma metabonomics study on toxicity biomarker in rats treated with Euphorbia fischeriana based on LC-MS
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基于LC-MS的大戟治疗大鼠毒性生物标志物血浆代谢组学研究
DOI：
10.1002/bmc.3696
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发表时间：
2016
影响因子：
1.8
通讯作者：
Zhao Baosheng
中科院分区：
文献类型：
--
作者：
Wang Yingfeng;Man Hongxue;Gao Jian;Liu Xinfeng;Ren Xiaolei;Chen Jianxin;Zhang Jiayu;Gao Kuo;Li Zhongfeng;Zhao Baosheng
在中国，狼毒（LD）传统上用于治疗人类疾病。本研究应用基于LC-MS的血浆代谢谱分析来阐明LD乙醇提取物对大鼠的毒性作用。LD注射液以0.1、0.05、0.025和0 g kg-1体重/天的剂量通过腹腔注射给予大鼠。LD注射大鼠的丙氨酸氨基转移酶、直接胆红素、肌酐、血清β2微球蛋白和低密度脂蛋白的血液生化水平升高，这些组的总蛋白和白蛋白水平降低。采用主成分分析、偏最小二乘判别分析和正交投影-潜在结构判别分析（OPLS-DA）等多元统计分析方法对样本的代谢谱进行分析。注射LD的大鼠的代谢特征以剂量依赖性方式受到干扰。通过OPLS-DA，18种代谢产物可作为潜在的毒性生物标志物。此外，LD处理导致对甲酚、硫酸对甲酚、溶血磷脂酰乙醇胺（LPE）（18：0）、LPE（16：0）、溶血磷脂酰胆碱（16：0）和12-HETE浓度增加，马尿酸、胆酸和N-乙酰基-L-苯丙氨酸减少。这些结果表明，长期暴露于LD可引起脂质代谢和氨基酸代谢等紊乱，因此，代谢谱的分析有助于更好地了解LD的不良影响。版权所有© 2016约翰威利父子有限公司.
Lang‐du (LD) has been traditionally used to treat human diseases in China. Plasma metabolic profiling was applied in this study based on LC–MS to elucidate the toxicity in rats induced by injected ethanol extract of LD. LD injection was given by intraperitoneal injection at doses of 0.1, 0.05, 0.025 and 0 g kg−1body weight per day to rats. The blood biochemical levels of alanine aminotransferase, direct bilirubin, creatinine, serumβ2‐microglobulin and low‐density lipoprotein increased in LD‐injected rats, and the levels of total protein and albumin decreased in these groups. The metabolic profiles of the samples were analyzed by multivariate statistics analysis, including principal component analysis, partial least squares discriminant analysis and orthogonal projection to latent structures discriminate analysis (OPLS‐DA). The metabolic characters in rats injected with LD were perturbed in a dose‐dependent manner. By OPLS‐DA, 18 metabolites were served as the potential toxicity biomarkers. Moreover, LD treatment resulted in an increase in thep‐cresol,p‐cresol sulfate, lysophosphatidylethanolamine (LPE) (18:0), LPE (16:0), lysophosphatidylcholine (16:0) and 12‐HETE concentrations, and a decrease in hippuric acid, cholic acid andN‐acetyl‐l‐phenylalanine. These results suggested that chronic exposure to LD could cause a disturbance in lipids metabolism and amino acids metabolism, etc. Therefore, an analysis of the metabolic profiles can contribute to a better understanding of the adverse effects of LD. Copyright © 2016 John Wiley & Sons, Ltd.