Department of Public Health, Faculty of Medicine, University of Szeged, Szeged, Hungary,
Department of Biochemistry and Molecular Biology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.
Int J Nanomedicine. 2018 Nov 2;13:7061-7077. doi: 10.2147/IJN.S179159. eCollection 2018.
Titanium dioxide nanoparticles have numerous applications, resulting in human exposure. Nonetheless, available toxicological and safety data are insufficient regarding aspherical particles, such as rod-shaped nanoparticles.
In a combined in vitro-in vivo approach, cultured A549 lung alveolar adenocarcinoma cells were treated with approximately 15×65 nm TiO nanorod-containing medium, while young adult rats received the same substance by intratracheal instillation for 28 days in 5 and 18 mg/kg body-weight doses. Nanoparticle accumulation in the lungs and consequent oxidative stress, cell damage, and inflammation were assessed by biochemical and histopathological methods.
Titanium was detected in tissue samples by single-particle inductively coupled plasma mass spectrometry. Nanoparticles were visualized inside cultured A549 cells, within pulmonary macrophages, and in hilar lymph nodes of the rats. A549 cells showed dose-dependent oxidative stress and lethality, and the observed nanoparticle-laden endosomes suggested deranged lysosomal function and possible autophagy. Strongly elevated Ti levels were measured in the lungs of nanorod-treated rats and moderately elevated levels in the blood of the animals. Numerous cytokines, indicating acute and also chronic inflammation, were identified in the lung samples of TiO-exposed rodents.
Several signs of cell and tissue damage were detected in both the cultured alveolar cells and in treated rats' lungs. Rod-shaped nanoparticulate TiO may consequently be more harmful than has generally been supposed. The occupational health risk suggested by the results calls for improved safety measures.
二氧化钛纳米颗粒具有多种应用,导致人类暴露于其中。然而,对于非球形颗粒,如棒状纳米颗粒,目前可用的毒理学和安全性数据还不够充分。
在一项体外-体内联合研究中,用含有约 15×65nm TiO 纳米棒的培养基处理培养的 A549 肺肺泡腺癌细胞,同时将相同的物质通过气管内滴注给予年轻成年大鼠,连续 28 天,剂量分别为 5 和 18mg/kg 体重。通过生化和组织病理学方法评估纳米颗粒在肺部的积累以及由此产生的氧化应激、细胞损伤和炎症。
通过单颗粒电感耦合等离子体质谱法在组织样本中检测到钛。在培养的 A549 细胞、肺巨噬细胞和大鼠肺门淋巴结中观察到纳米颗粒。A549 细胞表现出剂量依赖性的氧化应激和细胞毒性,观察到的载有纳米颗粒的内体表明溶酶体功能紊乱和可能的自噬。在纳米棒处理大鼠的肺部中测量到强烈升高的 Ti 水平,在动物的血液中也测量到中度升高的 Ti 水平。在暴露于 TiO 的啮齿动物的肺样本中鉴定出许多细胞因子,表明存在急性和慢性炎症。
在培养的肺泡细胞和处理大鼠的肺部中都检测到了几种细胞和组织损伤的迹象。因此,棒状纳米颗粒 TiO 可能比通常认为的更具危害性。研究结果提示存在职业健康风险,需要采取改进的安全措施。