College of Pharmacy, Dongduk Women's University, 60, Hwarang-ro, 13-gil Seongbuk-gu, Seoul, 02748, Korea.
Korea Institute of Toxicology, KIT, Daejeon, 34114, Korea.
Arch Pharm Res. 2018 Nov;41(11):1108-1116. doi: 10.1007/s12272-018-1074-7. Epub 2018 Sep 3.
Toxicity and target organ distribution of cerium oxide nanoparticles (CeNPs) were investigated via single intravenous injection and single oral administration, respectively. Rats were sacrificed at 24 h after treatment with doses of 30 and 300 mg/kg, and cerium concentrations were measured in liver, kidney, spleen, lung, blood, urine and feces. Results revealed cerium levels in blood and tissues were considerably low in oral treated groups and most cerium was detected in feces, meaning CeNPs would not be absorbed in the gastro-intestinal system. Conversely, high concentrations of cerium were detected in all tissues of rats after intravenous injection. Liver and spleen were main target organs. Cerium levels in liver were 594.9 ± 95.3 μg/g tissue in 30 mg/kg treat group and 3741.7 ± 932.7 μg/g tissue in 300 mg/kg treat group. Cerium levels in spleen reached almost levels of liver. Cerium was also detected, that is relatively low compared to oral administration, in feces of rats treated via intravenous injection, that supports biliary excretion of CeNPs. Urine excretion of CeNPs was not detected in oral treatment and intravenous injection. In accordance with level of cerium distribution, toxicities based on hematology, serum biochemistry and histopathology were observed in rats treated by intravenous injection while no significance was revealed in orally treated groups.
通过单次静脉注射和单次口服分别研究了氧化铈纳米粒子(CeNPs)的毒性和靶器官分布。在 30 和 300mg/kg 剂量处理后 24 小时处死大鼠,测量肝脏、肾脏、脾脏、肺、血液、尿液和粪便中的铈浓度。结果表明,口服处理组血液和组织中的铈水平相当低,并且大多数铈在粪便中被检测到,这意味着 CeNPs 不会在胃肠道系统中被吸收。相反,静脉注射后,所有组织中都检测到大量的铈。肝脏和脾脏是主要的靶器官。在 30mg/kg 处理组中,肝脏中的铈含量为 594.9±95.3μg/g 组织,在 300mg/kg 处理组中为 3741.7±932.7μg/g 组织。脾脏中的铈水平几乎达到肝脏的水平。与口服给药相比,静脉注射给药的大鼠粪便中也检测到铈,这支持 CeNPs 的胆汁排泄。在口服处理和静脉注射处理中均未检测到 CeNPs 的尿液排泄。根据铈分布水平,静脉注射给药的大鼠表现出基于血液学、血清生物化学和组织病理学的毒性,而口服给药组则没有表现出显著差异。