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Titanium dioxide nanoparticles enhance thrombosis through triggering the phosphatidylserine exposure and procoagulant activation of red blood cells
Particle and Fibre Toxicology ( IF 10 ) Pub Date : 2021-08-04 , DOI: 10.1186/s12989-021-00422-1
Yiying Bian 1 , Han-Young Chung 2 , Ok-Nam Bae 3 , Kyung-Min Lim 4 , Jin-Ho Chung 5 , Jingbo Pi 1
Affiliation  

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. 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. 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.

中文翻译:

二氧化钛纳米粒子通过触发磷脂酰丝氨酸暴露和红细胞促凝激活增强血栓形成

锐钛矿二氧化钛 (TiO2) 纳米粒子 (NPs) 的生物医学应用不断扩大,引起了公众对其潜在健康危害的关注。在这里,我们证明了 TiO2 NPs 可以增加磷脂酰丝氨酸 (PS) 暴露和红细胞 (RBC) 的促凝活性,这可能有助于血栓形成。我们使用从健康男性志愿者身上新鲜分离的红细胞进行了体外研究。TiO2 NPs 暴露(≤ 25 μg/mL)诱导 PS 暴露和微泡 (MV) 生成,伴随着 RBC 的形态变化。虽然在暴露于 TiO2 NPs 后没有观察到 ROS 的产生,但细胞内钙增加并且 caspase-3 被激活,这会上调加扰酶活性,导致 PS 暴露。RBCs 暴露于 TiO2 NPs 可以增加促凝血活性,如通过加速凝血酶生成所测量的,增强红细胞-内皮细胞粘附和红细胞-红细胞聚集。确认体外红细胞的促凝激活,大鼠暴露于 TiO2 NPs(2 mg/kg 静脉注射)会增加静脉血栓形成模型中的血栓形成。总的来说,这些结果表明锐钛矿 TiO2 NPs 可能通过促进红细胞的促凝活性而具有促血栓形成的风险,这在其生物医学应用中需要引起注意。
更新日期:2021-08-04
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