As titanium dioxide (TiO(2)) nanoparticles are widely used commercially, their potential biosafety and metabolic mechanism needs to be fully explained. In this study, the cytotoxicity of homogeneous and weakly aggregated (< 100 nm) TiO(2) nanoparticles was investigated by analyzing the changes in metabolite profiles both in mouse fibroblast (L929) cells and their corresponding culture media using gas chromatograph with a time-of-flight mass spectrometry (GC/TOFMS)-based metabolomic strategy. With multivariate statistics analysis, satisfactory separations were observed in principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) models. Based on the variable importance in the OPLS-DA models, a series of differential metabolites were identified by comparison between TiO(2) nanoparticle-treated L929 cells or their corresponding culture media and the control groups. It was found that the major biochemical metabolism (carbohydrate metabolism) was suppressed in TiO(2) nanoparticle-treated L929 cells and their corresponding culture media. These results might account for the serious damage to energy metabolism in mitochondria and the increased cellular oxidation stress in TiO(2) nanoparticle-induced L929 cells. These results also suggest that the metabolomic strategy had a great potential in evaluating the cytotoxicity of TiO(2) nanoparticles and thus was very helpful in understanding its underlying molecular mechanisms.

译文

由于二氧化钛 (TiO(2)) 纳米颗粒在商业上被广泛使用,因此需要充分解释其潜在的生物安全性和代谢机理。在这项研究中,通过使用气相色谱仪分析小鼠成纤维细胞 (L929) 细胞及其相应培养基中代谢物谱的变化,研究了均质和弱聚集 (< 100  nm) TiO(2) 纳米颗粒的细胞毒性飞行时间质谱 (GC/TOFMS) 基于代谢组学策略。通过多元统计分析,在主成分分析 (PCA) 和正交偏最小二乘判别分析 (OPLS-DA) 模型中观察到令人满意的分离。基于OPLS-DA模型中的可变重要性,通过将TiO(2) 纳米颗粒处理的L929细胞或其相应的培养基与对照组进行比较,鉴定出一系列差异代谢物。发现在TiO(2) 纳米颗粒处理的L929细胞及其相应的培养基中,主要的生化代谢 (碳水化合物代谢) 受到抑制。这些结果可能解释了线粒体能量代谢的严重损害以及TiO(2) 纳米颗粒诱导的L929细胞中细胞氧化应激的增加。这些结果还表明,代谢组学策略在评估TiO(2) 纳米颗粒的细胞毒性方面具有巨大潜力,因此对理解其潜在的分子机制非常有帮助。

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