Zoophysiology, Department of Biological Sciences, Aarhus University, Denmark.
Toxicol Appl Pharmacol. 2013 Jan 15;266(2):276-88. doi: 10.1016/j.taap.2012.10.014. Epub 2012 Nov 8.
This study describes the distribution of intravenously injected polyacrylic acid (PAA) coated γ-Fe(2)O(3) NPs (10 mg kg(-1)) at the organ, cellular and subcellular levels in healthy BALB/cJ mice and in parallel addresses the effects of NP injection on kidney function, blood pressure and vascular contractility. Magnetic resonance imaging (MRI) and transmission electron microscopy (TEM) showed accumulation of NPs in the liver within 1h after intravenous infusion, accommodated by intracellular uptake in endothelial and Kupffer cells with subsequent intracellular uptake in renal cells, particularly the cytoplasm of the proximal tubule, in podocytes and mesangial cells. The renofunctional effects of NPs were evaluated by arterial acid-base status and measurements of glomerular filtration rate (GFR) after instrumentation with chronically indwelling catheters. Arterial pH was 7.46±0.02 and 7.41±0.02 in mice 0.5 h after injections of saline or NP, and did not change over the next 12 h. In addition, the injections of NP did not affect arterial PCO(2) or [HCO(3)(-)] either. Twenty-four and 96 h after NP injections, the GFR averaged 0.35±0.04 and 0.35±0.01 ml min(-1) g(-1), respectively, values which were statistically comparable with controls (0.29±0.02 and 0.33±0.1 ml(-1) min(-1) 25 g(-1)). Mean arterial blood pressure (MAP) decreased 12-24 h after NP injections (111.1±11.5 vs 123.0±6.1 min(-1)) associated with a decreased contractility of small mesenteric arteries revealed by myography to characterize endothelial function. In conclusion, our study demonstrates that accumulation of superparamagnetic iron oxide nanoparticles does not affect kidney function in healthy mice but temporarily decreases blood pressure.
本研究描述了静脉注射聚(丙稀酸)包裹γ-Fe(2)O(3)纳米粒子(10mg/kg)在健康 BALB/cJ 小鼠体内的器官、细胞和亚细胞水平的分布,并同时探讨了纳米粒子注射对肾功能、血压和血管收缩性的影响。磁共振成像(MRI)和透射电子显微镜(TEM)显示,纳米粒子在静脉输注后 1 小时内积聚在肝脏中,被内皮细胞和库普弗细胞内摄取,随后被肾细胞内摄取,特别是近端肾小管的细胞质、足细胞和系膜细胞。通过动脉酸碱状态和用慢性留置导管测量肾小球滤过率(GFR)来评估纳米粒子的肾功能效应。注射生理盐水或纳米粒子后 0.5 小时,小鼠的动脉 pH 值分别为 7.46±0.02 和 7.41±0.02,在接下来的 12 小时内没有变化。此外,纳米粒子注射也不影响动脉 PCO(2)或[HCO(3)(-)]。注射纳米粒子后 24 和 96 小时,GFR 分别平均为 0.35±0.04 和 0.35±0.01ml min(-1) g(-1),与对照组相比统计学上无差异(0.29±0.02 和 0.33±0.1 ml(-1) min(-1) 25 g(-1))。纳米粒子注射后 12-24 小时平均动脉血压(MAP)下降(111.1±11.5 与 123.0±6.1 min(-1)),同时,通过肌电图测量,小肠系膜动脉的收缩性降低,这表明内皮功能受到影响。总之,我们的研究表明,超顺磁氧化铁纳米粒子的积聚不会影响健康小鼠的肾功能,但会暂时降低血压。