Pharmaceutical Sciences, University of Kentucky, Lexington, KY, USA.
Anatomical Sciences & Neurobiology, University of Louisville, Louisville, KY, USA.
Nanotoxicology. 2020 Aug;14(6):827-846. doi: 10.1080/17435390.2020.1770887. Epub 2020 Jun 18.
Prior studies showed nanoparticle clearance was different in C57BL/6 versus BALB/c mice, strains prone to Th1 and Th2 immune responses, respectively. : Assess nanoceria (cerium oxide, CeO nanoparticle) uptake time course and organ distribution, cellular and oxidative stress, and bioprocessing as a function of mouse strain. : C57BL/6 and BALB/c female mice were i.p. injected with 10 mg/kg nanoceria or vehicle and terminated 0.5 to 24 h later. Organs were collected for cerium analysis; light and electron microscopy with elemental mapping; and protein carbonyl, IL-1β, and caspase-1 determination. : Peripheral organ cerium significantly increased, generally more in C57BL/6 mice. Caspase-1 was significantly elevated in the liver at 6 h, to a greater extent in BALB/c mice, suggesting inflammasome pathway activation. Light microscopy revealed greater liver vacuolation in C57BL/6 mice and a nanoceria-induced decrease in BALB/c but not C57BL/6 mice vacuolation. Nanoceria increased spleen lymphoid white pulp cell density in BALB/c but not C57BL/6 mice. Electron microscopy showed intracellular nanoceria particles bioprocessed to form crystalline cerium phosphate nanoneedles. Ferritin accumulation was greatly increased proximal to the nanoceria, forming core-shell-like structures in C57BL/6 but even distribution in BALB/c mice. : BALB/c mice were more responsive to nanoceria-induced effects, e.g. liver caspase-1 activation, reduced liver vacuolation, and increased spleen cell density. Nanoceria uptake, initiation of bioprocessing, and crystalline cerium phosphate nanoneedle formation were rapid. Ferritin greatly increased with a macrophage phenotype-dependent distribution. Further study will be needed to understand the mechanisms underlying the observed differences.
先前的研究表明，纳米颗粒的清除在 C57BL/6 与 BALB/c 两种小鼠之间存在差异，这两种小鼠分别倾向于产生 Th1 和 Th2 免疫反应。本研究旨在评估纳米氧化铈（CeO 纳米颗粒）的摄取时程和器官分布、细胞和氧化应激以及生物处理情况，并分析其与小鼠品系的关系。将 10mg/kg 的纳米氧化铈或载体通过腹腔注射的方式分别注入到 C57BL/6 和 BALB/c 雌性小鼠体内，然后在 0.5 至 24 小时后处死小鼠。收集器官以进行铈分析；使用元素映射进行光镜和电子显微镜检查；并测定蛋白质羰基、IL-1β 和半胱氨酸天冬氨酸蛋白酶-1。结果显示，外周器官中的铈含量显著增加，在 C57BL/6 小鼠中更为明显。在 6 小时时，肝脏中的半胱氨酸天冬氨酸蛋白酶-1显著升高，在 BALB/c 小鼠中升高更为明显，提示炎症小体途径被激活。光镜检查显示 C57BL/6 小鼠的肝脏空泡化更为明显，而 BALB/c 小鼠的空泡化则减少，纳米氧化铈可诱导这种变化。纳米氧化铈增加了 BALB/c 小鼠而不是 C57BL/6 小鼠脾脏淋巴白髓细胞的密度。电子显微镜显示，细胞内的纳米氧化铈颗粒被生物处理形成结晶磷酸铈纳米针。铁蛋白在靠近纳米氧化铈的部位大量积累，在 C57BL/6 小鼠中形成核壳样结构，而在 BALB/c 小鼠中则呈均匀分布。BALB/c 小鼠对纳米氧化铈诱导的效应更为敏感，例如肝组织半胱氨酸天冬氨酸蛋白酶-1的激活、肝脏空泡化减少以及脾脏细胞密度增加。纳米氧化铈的摄取、生物处理的启动以及结晶磷酸铈纳米针的形成非常迅速。铁蛋白大量增加，其分布具有巨噬细胞表型依赖性。需要进一步研究以了解观察到的差异的潜在机制。
