Integrated metabonomics analysis of the size-response relationship of silica nanoparticles-induced toxicity in mice
Integrated metabonomics analysis of the size-response relationship of silica nanoparticles-induced toxicity in mice
复制标题
二氧化硅纳米颗粒诱导小鼠毒性的尺寸响应关系的综合代谢组学分析
DOI：
10.1088/0957-4484/22/5/055101
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发表时间：
2011-02-04
期刊：
影响因子：
3.5
通讯作者：
Fan, Xiaohui
中科院分区：
文献类型：
--
作者：
Lu, Xiaoyan;Tian, Yu;Fan, Xiaohui
了解纳米结构与生物系统的潜在性质依赖性相互作用对纳米毒理学研究至关重要。本研究以粒径为30、70和300 nm的SiO2颗粒（SP30、SP 70和SP300）为模型材料，探讨了粒径与毒性的关系，并进一步揭示了其致伤机理。采用基于气相色谱-质谱联用（GC-MS）的集成代谢组学分析方法，结合模式识别方法，对SP30、SP 70和SP300处理小鼠肝组织和血清的生化组成进行分析。同时进行组织学检查和血清生化分析。三种不同大小的SP引起的毒性主要表现为肝细胞坏死、血清转氨酶升高和炎性细胞因子。此外，SP的毒性作用是剂量依赖性的每种粒度。对肝脏有毒性的SP30、SP 70和SP300剂量分别为10、40和200 mg kg − 1。在这项研究中，表面积比颗粒数量对SP30，SP 70和SP300在肝脏中的毒性影响更大。能量代谢、氨基酸代谢、脂质代谢和核苷酸代谢的紊乱可能归因于SP诱导的肝毒性。此外，未发现由不同SP大小的代谢产物谱引起的生物系统反应的重大差异。结果表明，纳米级和亚微米级SP均能引起相似程度的肝损伤，且损伤程度与剂量有关，其毒性机制可能基本相同。
Understanding the underlying properties-dependent interactions of nanostructures with biological systems is essential to nanotoxicological research. This study investigates the relationship between particle size and toxicity, and further reveals the mechanism of injury, using silica particles (SP) with diameters of 30, 70, and 300 nm (SP30, SP70, and SP300) as model materials. The biochemical compositions of liver tissues and serum of mice treated with SP30, SP70, and SP300 were analyzed by integrated metabonomics analysis based on gas chromatography–mass spectrometry (GC–MS) and in combination with pattern recognition approaches. Histopathological examinations and serum biochemical analysis were simultaneously performed. The toxicity induced by three different sizes of SP mainly involved hepatocytic necrosis, increased serum aminotransferase, and inflammatory cytokines. Moreover, the toxic effects of SP were dose-dependent for each particle size. The doses of SP30, SP70, and SP300 that were toxic to the liver were 10, 40, and 200 mg kg − 1, respectively. In this study, surface area has a greater effect than particle number on the toxicity of SP30, SP70, and SP300 in the liver. The disturbances in energy metabolism, amino acid metabolism, lipid metabolism, and nucleotide metabolism may be attributable to the hepatotoxicity induced by SP. In addition, no major differences were found in the response of biological systems caused by the different SP sizes among the metabolite profiles. The results suggest that not only nano-sized but also submicro-sized SP can cause similar extents of liver injury, which is dependent on the exposure dose, and the mechanism of toxicity may be almost the same.