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超顺磁性氧化铁和二氧化硅纳米粒子对肺细胞细胞器的体外细胞毒性研究。

In vitro cytotoxicity study of superparamagnetic iron oxide and silica nanoparticles on pneumocyte organelles.

机构信息

Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del IPN (CINVESTAV-IPN), Ciudad de México, Mexico.

Yale University School of Medicine, Department of Laboratory Medicine, New Haven, Connecticut, USA.

出版信息

Toxicol In Vitro. 2021 Apr;72:105071. doi: 10.1016/j.tiv.2020.105071. Epub 2020 Dec 29.

Abstract

Inhalation is the main route of nanoparticles (NP) exposure during manufacturing. Although many mechanisms of toxicity have been described, the interaction of NP with relevant pneumocytes organelles is not widely understood. Considering that the physicochemical properties of NP influence their toxicological responses, the objective of this study was to evaluate whether exposure to different NP, crystalline FeO NP and amorphous SiO NP could alter pneumocytes organelles in alveolar epithelial cells. To achieve this goal, cell viability, ultrastructural changes, lysosomal damage, mitochondrial membrane potential (MMP), lipid droplets (LD) formation and cytokines production were evaluated by MTT, electron microscopy, lysotracker red staining, JC-1, Oil Red staining and Milliplex® assay respectively. Both NP were observed within lamellar bodies (LB), lysosomes, and cytoplasm causing morphological changes. Exposure to SiO NP at 6 h induced lysosomal activation, but not FeO NP. MMP decreased and LD increased at the highest concentrations after both NP exposure. Pro-inflammatory cytokines were released only after SiO NP exposure at 48 h. These results indicate that SiO NP have a greater impact than FeO NP on organelles responsible for energy, secretion, degradation and metabolism in pneumocytes leading to the development of respiratory disorders or the exacerbation of preexisting conditions. Therefore, the established biocompatibility for amorphous NP has to be reconsidered.

摘要

吸入是制造过程中纳米颗粒(NP)暴露的主要途径。尽管已经描述了许多毒性机制,但 NP 与相关的肺细胞细胞器的相互作用尚未得到广泛理解。考虑到 NP 的物理化学性质会影响其毒理学反应,本研究的目的是评估暴露于不同的 NP,结晶 FeO NP 和非晶态 SiO NP 是否会改变肺泡上皮细胞中的肺细胞细胞器。为了实现这一目标,通过 MTT、电子显微镜、溶酶体红色染色、JC-1、油红染色和 Milliplex®分析分别评估细胞活力、超微结构变化、溶酶体损伤、线粒体膜电位(MMP)、脂质滴(LD)形成和细胞因子产生。两种 NP 均在板层小体(LB)、溶酶体和细胞质中被观察到,导致形态发生变化。SiO NP 在 6 小时时诱导溶酶体激活,但 FeO NP 没有。暴露于两种 NP 后,MMP 在最高浓度时降低,LD 在最高浓度时增加。只有在 SiO NP 暴露 48 小时后才会释放促炎细胞因子。这些结果表明,SiO NP 对肺细胞中负责能量、分泌、降解和代谢的细胞器的影响大于 FeO NP,导致呼吸障碍的发展或现有状况的恶化。因此,必须重新考虑对非晶态 NP 的既定生物相容性。

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