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Global metabolomics approach in in vitro and in vivo models reveals hepatic glutathione depletion induced by amorphous silica nanoparticles
Chemico-Biological Interactions ( IF 4.7 ) Pub Date : 2018-07-29 , DOI: 10.1016/j.cbi.2018.07.013
Nivedita Chatterjee , Jaeseong Jeong , Dahye Yoon , Suhkmann Kim , Jinhee Choi

The present study aimed to investigate the mechanisms involved in amorphous silica nanoparticles (aSiNPs)-mediated hepatotoxicity through the evaluation of changes in global metabolomics in in vitro and in vivo systems. 1H NMR-based non-targeted global metabolomics and biochemical approaches were conducted in an aSiNPs-treated human hepatoma cell line (HepG2) and in ICR mice liver. The non-targeted NMR-based metabolomic analysis, followed by pathway analysis, revealed the perturbation of glutathione metabolism and the depletion of the glutathione pool after aSiNPs treatment in both in vitro (HepG2 cells) and in vivo systems. The total glutathione level, glutathione-S-transferase enzyme activity, and antioxidant gene expression strongly corroborated the metabolomic analysis results. The in vitro results were further supported by the in vivo data, specifically for metabolites profiling (Pearson Correlation coefficient is 0.462 (p = 0.026)). Furthermore, the depletion of glutathione, the formation of NADPH oxidase-mediated reactive oxygen species, and oxidative stress were evident in aSiNPs-treated HepG2 cells. Overall, the suppression of glutathione metabolism and oxidative stress are among the principal causes of aSiNPs-mediated hepatotoxicity.



中文翻译:

体外体内模型的整体代谢组学方法揭示了无定形二氧化硅纳米颗粒诱导的肝谷胱甘肽耗竭

本研究旨在通过评估体外体内系统中整体代谢组学的变化来研究无定形二氧化硅纳米粒子(aSiNPs)介导的肝毒性的机制。在aSiNPs处理的人肝癌细胞系(HepG2)和ICR小鼠肝脏中进行了基于1 H NMR的非靶向全局代谢组学和生化方法。基于非靶向NMR的代谢组学分析,然后进行通路分析,揭示了在体外(HepG2细胞)和体内进行aSiNPs处理后谷胱甘肽代谢的扰动和谷胱甘肽池的消耗。系统。总谷胱甘肽水平,谷胱甘肽-S-转移酶活性和抗氧化剂基因表达强烈证实了代谢组学分析结果。的体外结果由进一步支持体内数据,专门用于代谢物谱(皮尔逊相关系数为0.462(p值= 0.026))。此外,在aSiNPs处理的HepG2细胞中,谷胱甘肽的消耗,NADPH氧化酶介导的活性氧的形成以及氧化应激是明显的。总体而言,谷胱甘肽代谢和氧化应激的抑制是aSiNPs介导的肝毒性的主要原因。

更新日期:2018-07-29
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