Kulich Pavel, Marvanová Soňa, Skoupý Radim, Škorič Miša, Vysloužil Jan, Šerý Omar, Mikuška Pavel, Alexa Lukáš, Coufalík Pavel, Křůmal Kamil, Moravec Pavel, Večeřa Zbyněk, Machala Miroslav
Department of Pharmacology and Toxicology, Veterinary Research Institute, Brno, Czech Republic.
Institute of Scientific Instruments, Czech Academy of Sciences, Brno, Czech Republic.
J Appl Toxicol. 2025 Jun;45(6):1004-1018. doi: 10.1002/jat.4759. Epub 2025 Feb 11.
TiO nanoparticles (NPs) are extensively used in various applications, highlighting the importance of ongoing research into their effects. This work belongs among rare whole-body inhalation studies investigating the effects of TiO NPs on mice. Unlike previous studies, the concentration of TiO NPs in the inhalation chamber (130.8 μg/m) was significantly lower. This 11-week study on mice confirmed in vivo the presence of TiO NPs in lung macrophages and type II pneumocytes including their intracellular localization by using the electron microscopy and the state-of-the-art methods detecting NPs' chemical identity/crystal structure, such as the energy-dispersed X-ray spectroscopy (EDX), cathodoluminescence (CL), and detailed diffraction pattern analysis using powder nanobeam diffraction (PNBD). For the first time in inhalation study in vivo, the alterations in erythrocyte morphology with evidence of echinocytes and stomatocytes, accompanied by iron accumulation in spleen, liver, and kidney, are reported following NP's exposure. Together with the histopathological evidence of hyperaemia in the spleen and kidney, and haemosiderin presence in the spleen, the finding of NPs containing iron might suggest the increased decomposition of damaged erythrocytes. The detection of TiO NPs on erythrocytes through CL analysis confirmed their potential systemic availability. On the contrary, TiO NPs were not confirmed in other organs (spleen, liver, and kidney); Ti was detected only in the kidney near the detection limit.
二氧化钛纳米颗粒(NPs)被广泛应用于各种领域,这凸显了对其影响进行持续研究的重要性。这项工作属于罕见的关于二氧化钛纳米颗粒对小鼠影响的全身吸入研究。与之前的研究不同,吸入舱内二氧化钛纳米颗粒的浓度(130.8μg/m)显著更低。这项对小鼠进行的为期11周的研究通过电子显微镜以及检测纳米颗粒化学特性/晶体结构的先进方法,如能量色散X射线光谱(EDX)、阴极发光(CL)和使用粉末纳米束衍射(PNBD)的详细衍射图谱分析,在体内证实了肺巨噬细胞和II型肺细胞中存在二氧化钛纳米颗粒及其细胞内定位。在体内吸入研究中首次报告,纳米颗粒暴露后红细胞形态发生改变,出现棘形红细胞和口形红细胞,同时脾脏、肝脏和肾脏中有铁积累。连同脾脏和肾脏充血的组织病理学证据以及脾脏中含铁血黄素的存在,含有铁的纳米颗粒的发现可能表明受损红细胞的分解增加。通过CL分析在红细胞上检测到二氧化钛纳米颗粒证实了它们潜在的全身可利用性。相反,在其他器官(脾脏、肝脏和肾脏)中未证实存在二氧化钛纳米颗粒;仅在肾脏中检测到钛,接近检测限。