Toxicity of Aluminum Silicates Used in Hemostatic Dressings Toward Human Umbilical Veins Endothelial Cells, HeLa Cells, and RAW267.4 Mouse Macrophages
Toxicity of Aluminum Silicates Used in Hemostatic Dressings Toward Human Umbilical Veins Endothelial Cells, HeLa Cells, and RAW267.4 Mouse Macrophages
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DOI：
10.1097/ta.0b013e3182033579
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发表时间：
2011-09-01
影响因子：
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通讯作者：
Kheirabadi, Bijan S.
中科院分区：
文献类型：
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作者：
Bowman, Phillip D.;Wang, Xinyu;Kheirabadi, Bijan S.
背景：硅酸铝已被用于控制严重外伤后的出血。 QuikClot (QC) 是第一个此类产品，WoundStat (WS) 是最新的产品。我们最近观察到，当WS用于止血时会导致血管血栓形成。本研究调查了 WS 在可能接触该矿物质的不同细胞类型中的细胞毒性，并将结果与其他矿物质如膨润土、高岭土和 QuikClot ACS+ (QC+) 进行了比较。方法：将人脐静脉内皮细胞 (HUVEC)、HeLa 细胞和 RAW267.4 小鼠巨噬细胞样细胞 (RAW) 直接与不同浓度的每种矿物质一起孵育 24 小时。使用 AlamarBlue 荧光技术通过代谢测定细胞活力。在另一项实验中，通过带有聚碳酸酯过滤器（0.4μm孔径）的Transwell插入物将矿物质暴露于HUVEC，以防止细胞和矿物质之间的直接接触，以确定直接接触或从矿物质中浸出化合物是否会导致细胞毒性。结果：将HUVEC和RAW细胞与1至100μg/mL的矿物质一起孵育24小时会产生不同的毒性。 WS的细胞毒性与膨润土相当，高于高岭土和QC+。在 100 μg/mL WS 或膨润土存在下，两种细胞类型均无法存活 24 小时。然而，这些矿物质对 HeLa 细胞的活力几乎没有影响。在第二个 HUVEC 实验中，将这些化合物置于 Transwell 插入物中的浓度提高 10 倍，但细胞活力并未降低。这一结果表明，有毒物质的浸出或矿物质的离子交换特性与营养物质的结合不会引起毒性。结论：虽然硅酸铝似乎对上皮细胞相对无害，但它们都对内皮细胞和巨噬细胞产生了一定的毒性。在同等剂量下，WS 和膨润土的毒性分别明显高于 QC+ 中存在的高岭土和沸石。细胞毒性作用似乎是由矿物质与伤口中存在的细胞直接接触引起的。这些数据表明，未来矿物止血剂的清除应该需要比当前食品和药物管理局的要求更广泛的细胞毒性测试。
Background: Aluminum silicates have been used to control bleeding after severe traumatic injury. QuikClot (QC) was the first such product, and WoundStat (WS) is the most recent. We recently observed that WS caused vascular thrombosis when applied to stop bleeding. This study investigated the cellular toxicity of WS in different cell types that may be exposed to this mineral and compared the results with other minerals such as bentonite, kaolin, and QuikClot ACS+ (QC +).Methods: Human umbilical vein endothelial cells (HUVEC), HeLa cells, and RAW267.4 mouse macrophage-like cells (RAW) were incubated directly with different concentrations of each mineral for 24 hours. Cell viability was determined metabolically using the AlamarBlue fluorescent technique. In another experiment, minerals were exposed to HUVEC via Transwell inserts with a polycarbonate filter (0.4-mu m pore size) to prevent direct contact between cells and minerals for determining whether direct exposure or leaching compounds from minerals cause cytotoxicity.Results: Incubation of HUVEC and RAW cells with 1 to 100 mu g/mL of the minerals for 24 hours resulted in differential toxicities. The cytotoxicity of WS was equal to that of bentonite and higher than kaolin and QC+. Neither cell type survived for 24 hours in the presence of 100 mu g/mL WS or bentonite. These minerals, however, had little effect on the viability of HeLa cells. In the second HUVEC experiment, a 10 times higher concentration of these compounds placed in Transwell inserts yielded no decrease in cell viability. This result indicates that leaching toxicants or binding of nutrients by the ion-exchange properties of minerals did not cause the toxicity.Conclusions: Although aluminum silicates seem relatively innocuous to epithelial cells, all produced some toxicity toward endothelial cells and macrophages. WS and bentonite were significantly more toxic than kaolin and zeolite present in QC+, respectively, at equivalent doses. The cytotoxic effect seemed to be caused by the direct contact of the minerals with the cells present in wounds. These data suggest that the future clearance of mineral-based hemostatic agents should require more extensive cytotoxicity testing than the current Food and Drug Administration requirements.