NMR spectroscopic-based metabonomic investigation on the acute biochemical effects induced by Ce(NO3)3 in rats.
NMR spectroscopic-based metabonomic investigation on the acute biochemical effects induced by Ce(NO3)3 in rats.
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DOI：
10.1016/j.jinorgbio.2005.07.014
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发表时间：
2005-11
影响因子：
3.9
通讯作者：
Huifeng Wu;Xiaoyu Zhang;Peiqiu Liao;Zhongfeng Li;Weisheng Li;Xiaojing Li;Yijie Wu;F. Pei
中科院分区：
文献类型：
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作者：
Huifeng Wu;Xiaoyu Zhang;Peiqiu Liao;Zhongfeng Li;Weisheng Li;Xiaojing Li;Yijie Wu;F. Pei
本文应用基于高分辨~ 1H NMR谱的综合代谢组学方法研究了Ce（NO_3）_3对大鼠的急性生化效应。雄性Wistar大鼠分为8组，分别用氯化汞（HgCl_2）、氢溴酸溴化2-溴乙胺（HCl_3）、四氯化碳（CCl_4）、异硫氰酸萘酯（ANIT）和Ce（NO_3）_3（2、10和50 mg/kg体重）腹腔注射。在Ce（NO3）3染毒48 h后，收集尿液，采集血清和肝、肾组织标本。还对所有组织和血浆样本进行了组织学和血浆临床化学分析。通过600 MHz 1H NMR光谱分析尿液和血清样品。所有的1H NMR谱数据处理和分析，采用主成分分析或聚类分析，显示时间和剂量依赖性的生化变化由Ce（NO3）3。Ce（NO3）3处理动物的尿1H NMR谱的代谢特征显示，氧化三甲胺（TMAO）、二甲胺（DMA）、二甲基甘氨酸（DMG）、牛磺酸（Tau）和氨基酸（缬氨酸、亮氨酸和异亮氨酸）增加，柠檬酸盐减少。血清1H NMR谱分析显示丙酮、乙酰乙酸、乳酸和肌酐水平升高。这些结果表明肝线粒体脂肪酸β-氧化损伤和肾脏病变。本工作说明了基于NMR的代谢组学方法在研究稀土诱导的生化效应方面的高可靠性。
An integrated metabonomic approach based on high-resolution1H NMR spectroscopy has been applied to the investigation of the acute biochemical effects caused by Ce(NO3)3in rats. Male Wistar rats were separated into 8 groups and each was treated with one of following compounds, mercury II chloride (HgCl2), 2-bromoethanamine hydrobromide (BEA), carbon tetrachloride (CCl4), α-naphthylisothiocyanate (ANIT), and three doses of Ce(NO3)3(i.p. 2, 10 and 50mg/kg body weight). Urine was collected over a 48-h time course, and serum and tissue samples (liver and kidney) were gained after exposure to Ce(NO3)3for 48h. Histopathology and plasma clinical chemistry were also performed for all the tissue and plasma samples. Urine and serum samples were analyzed by 600MHz1H NMR spectroscopy. All the1H NMR spectra were data-processed and analyzed using principal components analysis or hierarchical clustering analysis to show the time- and dose-dependent biochemical variations induced by Ce(NO3)3. Metabolic profiles of urinary1H NMR spectra from animals treated with Ce(NO3)3exhibited an increase in trimethylamine N-oxide (TMAO), dimethylamine (DMA), dimethylglycine (DMG), taurine (Tau) and amino acids (valine, leucine and isoleucine), together with a decrease in citrate. The1H NMR spectral analysis of serum presented the elevation of acetone, acetoacetate, lactate and creatinine levels. These findings indicated the impairment of fatty acid β-oxidation in liver mitochondria and renal lesions. This work illustrates the high reliability of NMR-based metabonomic approach on the study of the biochemical effects induced by rare earths.