Abstract

The combination effect of co-exposed different types of nanomaterials is little known although humans are generally exposed to a mixture of nanomaterials from urban ultrafine particles or industrial nanomaterials. Herein, we evaluated the combined effect of nanoparticles (NPs) using three types of NPs in different inflammogenic categories: carbon black (CB), nickel oxide (NiO), and copper oxide (CuO). A single type of NPs or NPs in combination was intratracheally instilled into the lungs of rats and the bronchoalveolar lavage fluid (BALF) was analyzed at 24 h after instillation to evaluate the acute inflammogenic potential. The percentage of neutrophils in BALF was selected as a toxicity endpoint and the potential for reactive oxygen species (ROS) generation, dose–response of the combined effect, sequential treatment of CB and NiO, and uptake of NiO to alveolar macrophages after combined treatment of CB and NiO were evaluated for the mechanism of the combined effect. Co-exposure of CuO and NiO showed an additive effect on the percentage of neutrophils and ROS generation potential, which implies that the physicochemical properties of each NP are not influenced by the other type. While CB exerted an antagonistic effect on the percentage of neutrophils in combined treatment with CuO or NiO. The antagonistic effect of CB was due to the scavenging activity of the ROS generated by the CuO and NiO rather than the competition in cellular uptake to target cells (i.e. alveolar macrophages), which highlight the importance of the combined effect of NPs in the risk assessment.

摘要

尽管人类通常暴露于城市超细颗粒或工业纳米材料的纳米材料的混合物中，但是共暴露不同类型的纳米材料的组合效果鲜为人知。在本文中，我们使用三种不同的发炎类别的NP来评估纳米颗粒（NP）的综合效果：炭黑（CB），氧化镍（NiO）和氧化铜（CuO）。气管内将单一类型的NP或NP组合气管内滴注到大鼠的肺中，并在滴注后24小时对支气管肺泡灌洗液（BALF）进行分析，以评估其急性发炎潜力。选择BALF中的中性粒细胞百分比作为毒性终点，并选择产生活性氧（ROS）的潜力，联合效应的剂量反应，CB和NiO的顺序治疗，并评估了CB和NiO联合处理后NiO对肺泡巨噬细胞的摄取，以评估其联合作用的机制。CuO和NiO的共同暴露对嗜中性粒细胞的百分比和ROS的产生潜力产生累加效应，这意味着每个NP的理化特性均不受另一种类型的影响。而CB在与CuO或NiO联合治疗时对中性粒细胞的百分比具有拮抗作用。CB的拮抗作用是由于CuO和NiO产生的ROS的清除活性，而不是细胞对靶细胞（即肺泡巨噬细胞）的摄取竞争，这突出了NP联合作用在风险评估中的重要性。 。