Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats

溶解 Zeta电位 核化学 化学 毒性 体内分布 动力学 体内 离子 纳米颗粒 材料科学 生物化学 体外 生物 纳米技术 物理 物理化学 生物技术 有机化学 量子力学
作者
Jong-Choon Kim,In-Chul Lee,Je‐Won Ko,Sung-Hyeuk Park,Je‐Oh Lim,In-Sik Shin,Changjong Moon,Sung-Hwan Kim,Jeong-Doo Her
出处
期刊:International Journal of Nanomedicine [Dove Medical Press]
卷期号:: 2883-2883 被引量:119
标识
DOI:10.2147/ijn.s106346
摘要

Abstract: Despite widespread use and prospective biomedical applications of copper nanoparticles (Cu NPs), their biosafety issues and kinetics remain unclear. Thus, the aim of this study was to compare the detailed in vivo toxicity of Cu NPs and cupric ions (CuCl 2 ; Cu ions) after a single oral dose. We determined the physicochemical characteristics of Cu NPs, including morphology, hydrodynamic size, zeta potential, and dissolution in gastric (pH 1.5), vehicle (pH 6.5), and intestinal (pH 7.8) conditions. We also evaluated the kinetics of Cu following a single equivalent dose (500 mg/kg) of Cu NPs and Cu ions. Cu NPs had highest dissolution (84.5%) only in gastric conditions when compared with complete dissolution of Cu ions under various physiological milieus. Kinetic analysis revealed that highest Cu levels in blood and tested organs of Cu NP-treated rats were 15%–25% lower than that of Cu ions. Similar to the case of Cu ions, Cu levels in the tested organs (especially liver, kidney, and spleen) of Cu NP-treated rats increased significantly when compared with the vehicle control. However, delay in reaching the highest level and biopersistence of Cu were observed in the blood and tested organs of Cu NP-treated rats compared with Cu ions. Extremely high levels of Cu in feces indicated that unabsorbed Cu NPs or absorbed Cu ions were predominantly eliminated through liver/feces. Cu NPs exerted apparent toxicological effects at higher dose levels compared with Cu ions and showed sex-dependent differences in mortality, biochemistry, and histopathology. Liver, kidney, and spleen were the major organs affected by Cu NPs. Collectively, the toxicity and kinetics of Cu NPs are most likely influenced by the release of Cu dissociated from Cu NPs under physiological conditions. Keywords: copper nanoparticles, cupric ions, comparative toxicity, toxicokinetics
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