Visalli Giuseppa, Facciolà Alessio, Iannazzo Daniela, Piperno Anna, Pistone Alessandro, Di Pietro Angela
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, Italy.
Department of Electronic Engineering, Industrial Chemistry and Engineering, University of Messina, Italy.
J Trace Elem Med Biol. 2017 Sep;43:153-160. doi: 10.1016/j.jtemb.2017.01.005. Epub 2017 Jan 20.
This study aimed to investigate the role of iron, used as a catalyst, in the biological response to pristine and functionalized multi-walled carbon nanotubes (p/fMWCNTs) with an iron content of 2.5-2.8%. Preliminarily, we assessed the pro-oxidant activity of MWCNTs-associated iron by an abiotic test. To evaluate iron bioavailability, we measured intracellular redox-active iron in A549 cells exposed to both MWCNT suspensions and to the cell medium preconditioned by MWCNTs, in order to assess the iron dissolution rate under physiological conditions. Moreover, in exposed cells, we detected ROS levels, 8-oxo-dG and mitochondrial function. The results clearly highlighted that MWCNTs- associated iron was not redox-active and that iron leakage did not occur under physiological conditions, including the oxidative burst of specialized cells. Despite this, in MWCNTs exposed cells, higher level of intracellular redox-active iron was measured in comparison to control and a significant time-dependent ROS increase was observed (P<0.01). Higher levels of 8-oxo-dG, a marker of oxidative DNA damage, and decreased mitochondrial function, confirmed the oxidative stress induced by MWCNTs. Based on the results we believe that oxidative damage could be attributable to the release of endogenous redox-active iron. This was due to the damage of acidic vacuolar compartment caused by endocytosis-mediated MWCNT internalization.
本研究旨在探讨作为催化剂的铁在对铁含量为2.5 - 2.8%的原始和功能化多壁碳纳米管(p/fMWCNTs)的生物反应中的作用。首先,我们通过非生物试验评估了与MWCNTs相关的铁的促氧化活性。为了评估铁的生物利用度,我们测量了暴露于MWCNT悬浮液以及经MWCNTs预处理的细胞培养基中的A549细胞内具有氧化还原活性的铁,以评估生理条件下的铁溶解速率。此外,在暴露的细胞中,我们检测了活性氧水平、8-氧代脱氧鸟苷和线粒体功能。结果清楚地表明,与MWCNTs相关的铁没有氧化还原活性,并且在生理条件下,包括特殊细胞的氧化爆发,不会发生铁泄漏。尽管如此,与对照组相比,在暴露于MWCNTs的细胞中,测量到更高水平的细胞内氧化还原活性铁,并且观察到活性氧随时间显著增加(P<0.01)。更高水平的8-氧代脱氧鸟苷(氧化DNA损伤的标志物)和线粒体功能下降,证实了MWCNTs诱导的氧化应激。基于这些结果,我们认为氧化损伤可能归因于内源性氧化还原活性铁的释放。这是由于内吞作用介导的MWCNT内化导致酸性液泡区室受损所致。