Titanium dioxide nanoparticles enhance thrombosis through triggering the phosphatidylserine exposure and procoagulant activation of red blood cells

Particle and Fibre Toxicology

Kyung-Min Lim¹  Ok-Nam Bae²  Jin-Ho Chung³  Han-Young Chung⁴  Yiying Bian⁵  Jingbo Pi⁵ 

[1] College of Pharmacy, Ewha Womans University;College of Pharmacy, Hanyang University;College of Pharmacy, Seoul National University;Department of Agricultural Biotechnology, and Center for Food Safety and Toxicology, Seoul National University;School of Public Health, China Medical University;

关键词: Titanium dioxide nanoparticles (TiO2 NPs);    Phosphatidylserine (PS) exposure;    Procoagulant activity;    Thrombosis;    Red blood cells (RBCs);   

DOI  :  10.1186/s12989-021-00422-1

来源: DOAJ

【 摘 要 】

Abstract Background Expanding biomedical application of anatase titanium dioxide (TiO2) nanoparticles (NPs) is raising the public concern on its potential health hazards. Here, we demonstrated that TiO2 NPs can increase phosphatidylserine (PS) exposure and procoagulant activity of red blood cells (RBCs), which may contribute to thrombosis. Results We conducted in vitro studies using RBCs freshly isolated from healthy male volunteers. TiO2 NPs exposure (≦ 25 μg/mL) induced PS exposure and microvesicles (MV) generation accompanied by morphological changes of RBCs. While ROS generation was not observed following the exposure to TiO2 NPs, intracellular calcium increased and caspase-3 was activated, which up-regulated scramblase activity, leading to PS exposure. RBCs exposed to TiO2 NPs could increase procoagulant activity as measured by accelerated thrombin generation, and enhancement of RBC-endothelial cells adhesion and RBC-RBC aggregation. Confirming the procoagulant activation of RBC in vitro, exposure to TiO2 NPs (2 mg/kg intravenously injection) in rats increased thrombus formation in the venous thrombosis model. Conclusion Collectively, these results suggest that anatase TiO2 NPs may harbor prothrombotic risks by promoting the procoagulant activity of RBCs, which needs attention for its biomedical application.

【 授权许可】

Unknown