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在体内暴露于二氧化钛纳米棒后,大鼠肺部、肾脏和中枢神经系统以及体外培养的星形胶质细胞中存在钛和毒性作用。

Presence of Titanium and Toxic Effects Observed in Rat Lungs, Kidneys, and Central Nervous System in vivo and in Cultured Astrocytes in vitro on Exposure by Titanium Dioxide Nanorods.

机构信息

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.

出版信息

Int J Nanomedicine. 2020 Dec 8;15:9939-9960. doi: 10.2147/IJN.S275937. eCollection 2020.

Abstract

BACKGROUND

Non-spherical titanium dioxide (TiO) nanoparticles have been increasingly applied in various biomedical and technological fields. Their toxicological characterization is, however, less complete than that of roundish nanoparticles.

MATERIALS AND METHODS

Anatase form TiO nanorods, ca. 15x65 nm in size, were applied to cultured astrocytes in vitro and to the airways of young adult Wistar rats in vivo in 5, 10, and 8 mg/kg BW dose for altogether 28 days. Presence of nanorods and cellular damage was investigated in the astrocytes and in rat lungs and kidneys. Functional damage of the nervous system was studied by electrophysiological methods.

RESULTS

The treated astrocytes showed loss of viability without detectable apoptosis. In rats, TiO nanorods applied to the airways reached the blood and various organs including the lungs, kidneys, and the central nervous system. In lung and kidney samples, nanorods were observed within (partly damaged) phagolysosomes and attached to organelles, and apoptotic cell death was also detected. In cortical and peripheral electrophysiological activity, alterations corresponding to energy shortage (resulting possibly from mitochondrial damage) and astrocytic dysfunction were detected. Local titanium levels and relative weight of the investigated organs, apoptotic cell death in the lungs and kidneys, and changes in the central and peripheral nervous activity were mostly proportional to the applied doses, and viability loss of the cultured astrocytes was also dose-dependent, suggesting causal relationship of treatments and effects.

CONCLUSION

Based on localization of the visualized nanorods, on neuro-functional changes, and on literature data, the toxic mechanism involved mitochondrial damage, oxidative stress, and apoptotic cell death. These indicate potential human toxicity and occupational risk in case of exposure to rod-shaped TiO nanoparticles.

摘要

背景

非球形二氧化钛(TiO)纳米粒子已越来越多地应用于各种生物医学和技术领域。然而,它们的毒理学特征描述不如圆形纳米粒子完整。

材料和方法

锐钛矿形式的 TiO 纳米棒,大小约为 15x65nm,用于体外培养的星形胶质细胞和体内年轻成年 Wistar 大鼠的气道中,剂量分别为 5、10 和 8mg/kgBW,共 28 天。研究了纳米棒在星形胶质细胞和大鼠肺和肾中的存在和细胞损伤。通过电生理方法研究了神经系统的功能损伤。

结果

处理后的星形胶质细胞表现出活力丧失,而没有检测到凋亡。在大鼠中,应用于气道的 TiO 纳米棒到达血液和各种器官,包括肺、肾和中枢神经系统。在肺和肾组织样本中,纳米棒被观察到在(部分受损的)吞噬溶酶体中,并附着在细胞器上,并且还检测到凋亡细胞死亡。在皮质和周围电生理活性中,检测到与能量短缺(可能由线粒体损伤引起)和星形胶质细胞功能障碍相对应的改变。局部钛水平和所研究器官的相对重量、肺和肾脏中的凋亡细胞死亡以及中枢和周围神经活动的变化与所应用的剂量大致成正比,并且培养的星形胶质细胞的活力丧失也与剂量有关,表明治疗和效果之间存在因果关系。

结论

基于可视化纳米棒的定位、神经功能变化和文献数据,所涉及的毒理机制包括线粒体损伤、氧化应激和凋亡细胞死亡。这些表明在暴露于棒状 TiO 纳米粒子的情况下,存在潜在的人类毒性和职业风险。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8998/7765755/0132ce94bf7c/IJN-15-9939-g0001.jpg

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