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采用混合三重四极杆飞行时间质谱联用非靶向代谢组学策略研究血清代谢物作为炭黑纳米颗粒诱导大鼠亚慢性毒性的生物标志物。

Characterization of serum metabolites as biomarkers of carbon black nanoparticles-induced subchronic toxicity in rats by hybrid triple quadrupole time-of-flight mass spectrometry with non-targeted metabolomics strategy.

机构信息

Department of Pharmaceutical Analysis, School of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei, 050017, PR China.

Department of Occupational and Environmental Health, the School of Public Health, Hebei Medical University, Shijiazhuang, Hebei, 050017, PR China.

出版信息

Toxicology. 2019 Oct 1;426:152268. doi: 10.1016/j.tox.2019.152268. Epub 2019 Aug 19.

Abstract

Carbon black nanoparticles (CBNPs) are one of atmospheric particles components and have been closely related with a series of lung diseases. It can reach the depths of the respiratory tract or even alveolar more easily than those micro-particles. Although some of its toxicities have been confirmed in animals or human bodies, the subchronic toxicity mechanism of CBNPs has been uncertain so far. Therefore, it is very necessary to establish a novel method and clarify the mechanism of subchronic toxicity caused by concentration adjustments of small molecule metabolites in vivo. In animal experiments, CB exposure, recovery and control group were set up. The concentration of CBNPs in chamber was 30.06 ± 4.42 mg/m. We developed a UHPLC-Q-TOF-MS/MS-based non-targeted metabolomic analysis strategy to analyze serum samples of rats. Then, differential metabolites in serum were found by multivariate data analysis and 39 potential biomarkers were identified. It was showed that main metabolic pathways associated with CBNPs exposure were hormones metabolism, amino acid metabolism, nucleotide metabolism and lipid metabolism. It is worth noting that long-term exposure to CBNPs had the greatest impact on steroid hormones biosynthesis so that the risk of infertility could increase. The results provided a new mechanistic insight into the metabolic alterations owing to CBNPs induced subchronic toxicity.

摘要

炭黑纳米颗粒(CBNPs)是大气颗粒成分之一,与一系列肺部疾病密切相关。与微颗粒相比,它更容易到达呼吸道深部甚至肺泡。尽管已经在动物或人体中证实了其某些毒性,但迄今为止,CBNPs 的亚慢性毒性机制仍不确定。因此,建立一种新的方法并阐明体内小分子代谢物浓度调整引起的亚慢性毒性机制是非常必要的。在动物实验中,设置了 CB 暴露、恢复和对照组。室内 CBNPs 的浓度为 30.06±4.42mg/m。我们开发了一种基于 UHPLC-Q-TOF-MS/MS 的非靶向代谢组学分析策略来分析大鼠的血清样本。然后,通过多变量数据分析发现了差异代谢物,并鉴定出 39 个潜在的生物标志物。结果表明,与 CBNPs 暴露相关的主要代谢途径是激素代谢、氨基酸代谢、核苷酸代谢和脂质代谢。值得注意的是,长期暴露于 CBNPs 对甾体激素生物合成的影响最大,这可能会增加不孕的风险。这些结果为 CBNPs 诱导的亚慢性毒性引起的代谢改变提供了新的机制见解。

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