Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: A rapid in vivo screening method for nanotoxicity

Lei, Ronghui; Wu, Cathy; Yang, Baofeng; Ma, Huazhai; Shi, Changhong; Wang, Quanjun; Wang, Qingxiu; Yuan, Ye; Ming-yang, Liao

doi:10.1016/j.taap.2008.06.026

Cited by 262 publications

(146 citation statements)

References 42 publications

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“…Another method for in vivo toxicity assessment is the examination of changes in the serum chemistry and cell type after exposure of nanoparticles [93]. Histopathology of the cell, tissue or organ after exposure is used to determine the toxicity level caused by a nanoparticle [94]. Histopathology examination has been used to nanoparticles' exposed tissues such as lung, eyes, brain, liver, kidneys, heart and spleen [93,95].…”

Section: In Vivo Toxicity Assessment Methodsmentioning

confidence: 99%

In vitro and in vivo toxicity assessment of nanoparticles

2017

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Nanotechnology has revolutionized gene therapy, diagnostics and environmental remediation. Their bulk production, uses and disposal have posed threat to the environment. With the appearance of these nanoparticles in the environment, their toxicity assessment is an immediate concern. This review is an attempt to summarize the major techniques used in cytotoxity determination. The review also presents a detailed and elaborative discussion on the toxicity imposed by different types of nanoparticles including carbon nanotubes, gold nanoparticles, silver nanoparticles, quantum dots, fullerenes, aluminium nanoparticles, zinc nanoparticles, iron nanoparticles, titanium nanoparticles and silica nanoparticles. It discusses the in vitro and in vivo toxological effects of nanoparticles on bacteria, microalgae, zebrafish, crustacean, fish, rat, mouse, pig, guinea pig, human cell lines and human. It also discusses toxological effects on organs such as liver, kidney, spleen, sperm, neural tissues, liver lysosomes, spleen macrophages, glioblastoma cells, hematoma cells and various mammalian cell lines. It provides information about the effects of nanoparticles on the gene-expression, growth and reproduction of the organisms.

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Section: In Vivo Toxicity Assessment Methodsmentioning

confidence: 99%

In vitro and in vivo toxicity assessment of nanoparticles

2017

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“…In the liver, the decrease in glucose levels and increase in lactate levels coupled with the alteration in succinate levels might reflect the effect of SiO 2 NPs on glycolysis and the mitochondrial Krebs cycle. 41 Phosphorylcholine and sn-glycero-3-phosphocholine are constituents of cell membranes and, thus, increased levels might be associated with the disruption of cellular membranes. 42 Another metabolic consequence of liver injury was that treatment with SiO 2 NPs resulted in the perturbation of amino acid metabolism, such as increased levels of threonine, phenylalanine, and lysine and a decrease in the level of glycine.…”

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confidence: 99%

Kupffer cell-mediated hepatic injury induced by silica nanoparticles in vitro and in vivo

Chen¹,

Yang²,

Sun³

2013

IJN

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Silica nanoparticles (SiO 2 NPs) have been shown to exert cytotoxic effects in hepatocytes and to cause liver injury. In the liver, Kupffer cells (KCs), as the resident macrophages, play an important role in the normal physiology and homeostasis of the liver. Nevertheless, few studies have attempted to clarify the role of KCs in hepatic injury induced by SiO 2 NPs. In this study, we treated Buffalo rat liver (BRL) cells with the supernatants of SiO 2 NP-stimulated KCs to determine KC-mediated hepatotoxicity and its underlying preliminary mechanism. We also examined the response of KCs and liver injury in vivo after the administration of SiO 2 NPs. The results showed that KCs stimulated by SiO 2 NPs release large amounts of reactive oxygen species, tumor necrosis factor-α and nitric oxide. After BRL cells were cultured with the supernatants of SiO 2 NP-stimulated KCs, the viability of BRL cells was reduced, and increases in aspartate aminotransferase and lactate dehydrogenase leakage were observed. Exposure to SiO 2 NPs in vivo caused KC hyperplasia, hepatic inflammation, and oxidative stress, which led to changes in the biochemical composition of the liver. These data suggest that SiO 2 NPs activate KCs to mediate hepatic injury and that the preliminary mechanism involves the release of bioactive substances from KCs.

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“…32 Although there are increasing numbers of in vitro studies, only few reports investigated the in vivo toxicity of Cu NPs. 17,[33][34][35] The acute toxicity study of Cu NPs and Cu ions has been previously conducted in mice. 17 The kinetics were evaluated limitedly on serum, kidney, and urine for 72 hours after exposure.…”

Section: Lee Et Almentioning

confidence: 99%

“…17,33 Repeated oral administration of Cu NPs to rats at 200 mg/kg/d for 5 days caused necrosis of hepatocytes and renal proximal tubules accompanied with hepatic and renal dysfunction. 33,34 In this study, a single oral dose of Cu NPs at 1,250 mg/kg in male rats and 2,500 mg/kg in female rats caused significant adverse effects on the histology of kidneys, liver, and spleen but not heart and lung. These histopathological changes were well supported by organ weight changes, including increased liver and kidney weights and decreased spleen weight.…”

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confidence: 99%

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

Lee¹,

Ko²,

Park³

et al. 2016

IJN

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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.

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Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: A rapid in vivo screening method for nanotoxicity

Cited by 262 publications

References 42 publications

In vitro and in vivo toxicity assessment of nanoparticles

In vitro and in vivo toxicity assessment of nanoparticles

Kupffer cell-mediated hepatic injury induced by silica nanoparticles in vitro and in vivo

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

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