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无机颗粒和纤维状物质引起的氧化和细胞毒性应激。

Oxidative and cytotoxic stress induced by inorganic granular and fibrous particles.

机构信息

Institute and Outpatient Clinic for Occupational and Social Medicine, Justus‑Liebig University, D‑35392 Giessen, Germany.

Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Giessen and Marburg, Campus Giessen, D‑35392 Giessen, Germany.

出版信息

Mol Med Rep. 2018 Jun;17(6):8518-8529. doi: 10.3892/mmr.2018.8923. Epub 2018 Apr 23.

Abstract

The hazards of granular and fibrous particles have been associated with the generation of reactive oxygen species (ROS), which in turn is often associated with physicochemical properties exhibited by these particles. In the present study, the ability of various types of fibrous and granular dusts to generate oxidative stress, and their cytotoxicity, was investigated. Biopersistent granular dusts employed in the present study included micro‑ and nanosized titanium dioxide with rutile or anatase crystal structure modifications. Additionally, glass fibres, chrysotile and crocidolite asbestos representative of fibrous dust were selected. Detailed characterisation of particles was performed using scanning electron microscopy, and the effect of exposure to these particles on cell viability and intracellular ROS generation was assessed by PrestoBlue and 2',7'‑dichlorofluorescein assays, respectively. A549 human lung epithelial adenocarcinoma cells were exposed to increasing concentrations (0.1‑10 µg/cm2) of particles and fibres for 24 h. Subsequently, the gene expression of X‑linked inhibitor of apoptosis (XIAP), superoxide dismutase (SOD)1 and SOD2 were analysed by reverse transcription‑quantitative polymerase chain reaction. All investigated granular particles induce ROS production in A549 lung carcinoma cells within 24 h. Hematite increased ROS production in a dose‑dependent manner. A concentration of >1 µg/cm2 TiO2 na with its disordered surface, demonstrated the greatest ability to generate ROS. Therefore, the crystalline surface structure of the particle may be considered as a determinant of the extent of ROS induction by the particle. Fibrous particle compared with granular particles were associated with a lower ability to generate ROS. Glass fibres did not significantly increase ROS production in A549 cells, but elevated gene expression of SOD2 was observed. The results demonstrated that in general, the ability of particles to generate ROS depends on their number and crystal phase. Therefore, the present study helps to understand the cause of particle toxicity.

摘要

颗粒状和纤维状颗粒的危害与活性氧(ROS)的产生有关,而 ROS 的产生又常常与这些颗粒表现出的物理化学性质有关。在本研究中,研究了各种类型的纤维状和颗粒状粉尘产生氧化应激的能力及其细胞毒性。本研究中使用的生物持久性颗粒状粉尘包括具有金红石或锐钛矿晶体结构修饰的微纳米级二氧化钛。此外,还选择了玻璃纤维、石棉纤维和青石棉作为纤维状粉尘的代表。通过扫描电子显微镜对颗粒进行了详细的表征,并通过 PrestoBlue 和 2',7'-二氯荧光素测定法分别评估了暴露于这些颗粒对细胞活力和细胞内 ROS 生成的影响。将 A549 人肺上皮腺癌细胞暴露于递增浓度(0.1-10 μg/cm2)的颗粒和纤维 24 h。随后,通过反转录定量聚合酶链反应分析了 X 连锁凋亡抑制剂(XIAP)、超氧化物歧化酶(SOD)1 和 SOD2 的基因表达。所有研究的颗粒状物质在 24 h 内均可诱导 A549 肺癌细胞产生 ROS。赤铁矿以剂量依赖性方式增加 ROS 的产生。具有无序表面的 TiO2 na 浓度>1μg/cm2 时,产生 ROS 的能力最强。因此,颗粒的结晶表面结构可被视为颗粒诱导 ROS 产生程度的决定因素。与颗粒状颗粒相比,纤维状颗粒产生 ROS 的能力较低。玻璃纤维不会显著增加 A549 细胞中的 ROS 产生,但观察到 SOD2 基因表达升高。结果表明,一般来说,颗粒产生 ROS 的能力取决于其数量和晶体相。因此,本研究有助于了解颗粒毒性的原因。

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