title: Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats.
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.
authors.affiliation: College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: In-Chul
authors.initials: IC
authors.lastname: Lee
authors.affiliation: College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Je-Won
authors.initials: JW
authors.lastname: Ko
authors.affiliation: College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Sung-Hyeuk
authors.initials: SH
authors.lastname: Park
authors.affiliation: College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Je-Oh
authors.initials: JO
authors.lastname: Lim
authors.affiliation: College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: In-Sik
authors.initials: IS
authors.lastname: Shin
authors.affiliation: College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Changjong
authors.initials: C
authors.lastname: Moon
authors.affiliation: Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeongeup, Republic of Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Gyeongnam Department of Environment and Toxicology, Korea Institute of Toxicology, Gyeongnam, Republic of Korea.
authors.forename: Jeong-Doo
authors.initials: JD
authors.lastname: Heo
authors.affiliation: College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju, Republic of Korea.
authors.forename: Jong-Choon
authors.initials: JC
authors.lastname: Kim
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003300:Copper / Q000633:toxicity*; D005753:Gastric Mucosa / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007477:Ions; D007700:Kinetics; D053768:Metal Nanoparticles / Q000633:toxicity* / Q000648:ultrastructure; D009928:Organ Specificity / Q000187:drug effects; D010316:Particle Size; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000187:drug effects; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D007477:Ions; D003300:Copper
keywords: comparative toxicity; copper nanoparticles; cupric ions; toxicokinetics