Mahmoud Abudayyak, Ezgi Öztaş, Merve Arici, Özhan Gül
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey.
Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, Istanbul, Turkey
Int J Toxicol. 2016 Jul;35(4):429-37. doi: 10.1177/1091581816648624. Epub 2016 May 13.
Worldwide researchers have rising concerns about magnesium-based materials, especially magnesium oxide (MgO) nanaoparticles, due to increasing usage as promising structural materials in various fields including cancer treatment. However, there is a serious lack of information about their toxicity at the cellular and molecular levels. In this study, the toxic potentials of MgO nanoparticles were investigated on liver (HepG2), kidney (NRK-52E), intestine (Caco-2), and lung (A549) cell lines. For the toxicological assessment, the following assays were used: the particle characterization by transmission electron microscopy, the determination of cellular uptake by inductively coupled plasma-mass spectrometry, MTT and neutral red uptake assays for cytotoxicity, comet assay for genotoxicity, and the determination of malondialdehyde (MDA), 8-hydroxydeoxyguanosine, protein carbonyl, and glutathione levels by enzyme-linked immune sorbent assays for the potential of oxidative damage and annexin V-fluorescein isothiocyanate (FITC) apoptosis detection assay with propidium iodide (PI) for apoptosis. Magnesium oxide nanoparticles were taken up by the cells depending on their concentration and agglomeration/aggregation potentials. Magnesium oxide nanoparticles induced DNA (≤14.27 fold) and oxidative damage. At a concentration of ≥323.39 µg/mL, MgO nanoparticles caused 50% inhibition in cell viability by 2 different cytotoxicity assays. The cell sensitivity to cytotoxic and genotoxic damage induced by MgO nanoparticles was ranked as HepG2 < A549 < Caco-2 < NRK-52E. Although it was observed that MgO nanoparticles induced apoptotic effects on the cells, apoptosis was not the main cell death. DNA damage, cell death, and oxidative damage effects of MgO nanoparticles should raise concern about the safety associated with their applications in consumer products.
由于镁基材料,尤其是氧化镁(MgO)纳米颗粒在包括癌症治疗在内的各个领域作为有前景的结构材料的使用日益增加,全球范围内的研究人员对其越来越关注。然而,关于它们在细胞和分子水平上的毒性,严重缺乏相关信息。在本研究中,研究了MgO纳米颗粒对肝(HepG2)、肾(NRK - 52E)、肠(Caco - 2)和肺(A549)细胞系的潜在毒性。为了进行毒理学评估,使用了以下检测方法:通过透射电子显微镜进行颗粒表征,通过电感耦合等离子体质谱法测定细胞摄取,用MTT和中性红摄取试验检测细胞毒性,用彗星试验检测遗传毒性,通过酶联免疫吸附测定法测定丙二醛(MDA)、8 - 羟基脱氧鸟苷、蛋白质羰基和谷胱甘肽水平以检测氧化损伤潜力,并用碘化丙啶(PI)结合膜联蛋白V - 异硫氰酸荧光素(FITC)凋亡检测试验检测凋亡。MgO纳米颗粒被细胞摄取的情况取决于其浓度以及团聚/聚集潜力。MgO纳米颗粒诱导了DNA损伤(≤14.27倍)和氧化损伤。在浓度≥323.39 µg/mL时,MgO纳米颗粒通过两种不同的细胞毒性试验导致细胞活力抑制50%。细胞对MgO纳米颗粒诱导的细胞毒性和遗传毒性损伤的敏感性排序为HepG2 < A549 < Caco - 2 < NRK - 52E。尽管观察到MgO纳米颗粒对细胞诱导了凋亡效应,但凋亡并非主要的细胞死亡方式。MgO纳米颗粒的DNA损伤、细胞死亡和氧化损伤效应应引起人们对其在消费品中应用安全性的关注。