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

In-Chul Lee,1 Je-Won Ko,1 Sung-Hyeuk Park,1 Je-Oh Lim,1 In-Sik Shin,1 Changjong Moon,1 Sung-Hwan Kim,2 Jeong-Doo Heo,3 Jong-Choon Kim1 1College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju, 2Jeonbuk Department of Inhalation Research, Korea Institute of Toxicol...

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Autores principales:	Lee IC, Ko JW, Park SH, Lim JO, Shin IS, Moon C, Kim SH, Heo JD, Kim JC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Copper nanoparticles cupric ions comparative toxicity toxicokinetics Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/3daa34aacd52497e80d86cee017b5225
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spelling	oai:doaj.org-article:3daa34aacd52497e80d86cee017b52252021-12-02T00:38:47ZComparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats1178-2013https://doaj.org/article/3daa34aacd52497e80d86cee017b52252016-06-01T00:00:00Zhttps://www.dovepress.com/comparative-toxicity-and-biodistribution-of-copper-nanoparticles-and-c-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013In-Chul Lee,1 Je-Won Ko,1 Sung-Hyeuk Park,1 Je-Oh Lim,1 In-Sik Shin,1 Changjong Moon,1 Sung-Hwan Kim,2 Jeong-Doo Heo,3 Jong-Choon Kim1 1College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju, 2Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeongeup, 3Gyeongnam Department of Environment and Toxicology, Korea Institute of Toxicology, Gyeongnam, Republic of Korea 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 (CuCl2; 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 Lee ICKo JWPark SHLim JOShin ISMoon CKim SHHeo JDKim JCDove Medical PressarticleCopper nanoparticlescupric ionscomparative toxicitytoxicokineticsMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2016, Iss default, Pp 2883-2900 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Copper nanoparticles cupric ions comparative toxicity toxicokinetics Medicine (General) R5-920
spellingShingle	Copper nanoparticles cupric ions comparative toxicity toxicokinetics Medicine (General) R5-920 Lee IC Ko JW Park SH Lim JO Shin IS Moon C Kim SH Heo JD Kim JC Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats
description	In-Chul Lee,1 Je-Won Ko,1 Sung-Hyeuk Park,1 Je-Oh Lim,1 In-Sik Shin,1 Changjong Moon,1 Sung-Hwan Kim,2 Jeong-Doo Heo,3 Jong-Choon Kim1 1College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju, 2Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeongeup, 3Gyeongnam Department of Environment and Toxicology, Korea Institute of Toxicology, Gyeongnam, Republic of Korea 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 (CuCl2; 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
format	article
author	Lee IC Ko JW Park SH Lim JO Shin IS Moon C Kim SH Heo JD Kim JC
author_facet	Lee IC Ko JW Park SH Lim JO Shin IS Moon C Kim SH Heo JD Kim JC
author_sort	Lee IC
title	Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats
title_short	Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats
title_full	Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats
title_fullStr	Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats
title_full_unstemmed	Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats
title_sort	comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/3daa34aacd52497e80d86cee017b5225
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Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats

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