Implication of oxidative stress in size-dependent toxicity of silica nanoparticles in kidney cells

Passagne, Isabelle; Morille, Marie; Rousset, Marine; Pujalté, Igor; L’Azou, B

doi:10.1016/j.tox.2012.05.010

Cited by 160 publications

(122 citation statements)

References 53 publications

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“…34,35 Furthermore, numerous metallic nanoparticles are selective nephrotoxicants that preferentially accumulate in the kidneys, further to induce renal injury. [36][37][38][39] It has been known for some time that chronic kidney diseases (CKD) are often accompanied by hypoxic, which may play an important pathogenic role in the development of renal damage; 40 whereas, no study has been performed concerning GNP interactions with hypoxic kidney cells, especially proximal tubules.…”

Section: Introductionmentioning

confidence: 99%

Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

Fan¹,

Li²,

Liu³

et al. 2014

IJN

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Background Gold nanoparticles (GNPs) can potentially be used in biomedical fields ranging from therapeutics to diagnostics, and their use will result in increased human exposure. Many studies have demonstrated that GNPs can be deposited in the kidneys, particularly in renal tubular epithelial cells. Chronic hypoxic is inevitable in chronic kidney diseases, and it results in renal tubular epithelial cells that are susceptible to different types of injuries. However, the understanding of the interactions between GNPs and hypoxic renal tubular epithelial cells is still rudimentary. In the present study, we characterized the cytotoxic effects of GNPs in hypoxic renal tubular epithelial cells. Results Both 5 nm and 13 nm GNPs were synthesized and characterized using various biophysical methods, including transmission electron microscopy, dynamic light scattering, and ultraviolet–visible spectrophotometry. We detected the cytotoxicity of 5 and 13 nm GNPs (0, 1, 25, and 50 nM) to human renal proximal tubular cells (HK-2) by Cell Counting Kit-8 assay and lactate dehydrogenase release assay, but we just found the toxic effect in the 5 nm GNP-treated cells at 50 nM dose under hypoxic condition. Furthermore, the transmission electron microscopy images revealed that GNPs were either localized in vesicles or free in the lysosomes in 5 nm GNPs-treated HK-2 cells, and the cellular uptake of the GNPs in the hypoxic cells was significantly higher than that in normoxic cells. In normoxic HK-2 cells, 5 nm GNPs (50 nM) treatment could cause autophagy and cell survival. However, in hypoxic conditions, the GNP exposure at the same condition led to the production of reactive oxygen species, the loss of mitochondrial membrane potential (ΔΨM), and an increase in apoptosis and autophagic cell death. Conclusion/significance Our results demonstrate that renal tubular epithelial cells presented different responses under normoxic and hypoxic environments, which provide an important basis for understanding the risks associated with GNP use–especially for the potential GNP-related therapies in chronic kidney disease patients.

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Section: Introductionmentioning

confidence: 99%

Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

Fan¹,

Li²,

Liu³

et al. 2014

IJN

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“…SiO 2 NP may induce cytotoxicity or apoptosis and lead to inflammation, DNA damage, or lipid peroxidation in various cell lines [16][17][18][19][20]. These adverse effects could be mediated by oxidative stress or/and the activation of stress-related signalling pathways [21,22].…”

Section: Introductionmentioning

confidence: 99%

“…These adverse effects could be mediated by oxidative stress or/and the activation of stress-related signalling pathways [21,22]. The toxicity appears to be dependent on NP size and surface [17,[23][24][25][26]. For instance, Li et al have demonstrated that SiO 2 NP with diameters of 19, 43, 68 and 498 nm cause cytotoxicity, increased reactive oxygen species (ROS) level, DNA damage and cell cycle arrest in HepG2 cells in a size-dependent manner [23].…”

Section: Introductionmentioning

confidence: 99%

Size and Cell Type Dependent Uptake of Silica Nanoparticles

Hsiao

Gramatke

Joksimovic

et al. 2014

J Nanomed Nanotechnol

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As silica nanoparticles (SiO 2 NP) gain increasing interest for medical applications it is important to understand their potential adverse effects for humans. Here we prepared well-defined core-shell fluorescently labelled SiO 2 NP of 15, 60 and 200 nm diameter and analyzed their cytotoxicity in THP-1 derived macrophages, A549 epithelial cells, HaCaT keratinocytes and NRK-52E kidney cells. We observed a size-dependent cytotoxicity in all cell types in serumfree conditions. HaCaT cells were least and macrophages or lung derived A549 cells were highly sensitive towards SiO 2 NP treatment. Differences in cytotoxicity could be correlated with different uptake rates. By using flow cytometry and confocal microscopy we quantified the uptake. Furthermore we used specific inhibitors for clathrin-and caveolinmediated endocytosis to elucidate the uptake mechanisms, which were found to be dependent on the NP size and the cell type. Clathrin-mediated endocytosis was involved in the uptake of SiO 2 NP of all sizes and was the major pathway for 60 nm or 200 nm SiO 2 NP. Caveolin-mediated endocytosis contributed to the uptake of 60 and 200 nm SiO 2 NP in THP-1 macrophages but only to uptake of 200 nm SiO 2 NP in A549. However, in the presence of serum all SiO 2 NP were non-toxic. The presence of serum furthermore could alter the uptake mechanism. In summary, this study demonstrates size-and cell type dependent differences in SiO 2 NP uptake and toxicity.

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“…[16][17][18] In all cases, the cytotoxic mechanism was suggested to involve pathways for oxidative stress and induction of apoptosis in the mitochondria. [19][20][21][22][23][24] On the other hand, administration of SiO 2 nanoparticles in rats did not have any toxic effect, except for formation of granuloma in the liver and spleen. 25 In the in vivo setting, when reconstituted nanoparticles in solution are administered via intravenous or intracerebral injection, nanoparticles would encounter proteins from blood or cerebrospinal fluid, which would influence their interactions at the cellular and tissue levels.…”

Section: Introductionmentioning

confidence: 90%

Analysis of SiO2 nanoparticles binding proteins in rat blood and brain homogenate

Shim¹,

Hulme²,

Maeng³

et al. 2014

IJN

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A multitude of nanoparticles, such as titanium oxide (TiO 2 ), zinc oxide, aluminum oxide, gold oxide, silver oxide, iron oxide, and silica oxide, are found in many chemical, cosmetic, pharmaceutical, and electronic products. Recently, SiO 2 nanoparticles were shown to have an inert toxicity profile and no association with an irreversible toxicological change in animal models. Hence, exposure to SiO 2 nanoparticles is on the increase. SiO 2 nanoparticles are routinely used in numerous materials, from strengthening filler for concrete and other construction composites, to nontoxic platforms for biomedical application, such as drug delivery and theragnostics. On the other hand, recent in vitro experiments indicated that SiO 2 nanoparticles were cytotoxic. Therefore, we investigated these nanoparticles to identify potentially toxic pathways by analyzing the adsorbed protein corona on the surface of SiO 2 nanoparticles in the blood and brain of the rat. Four types of SiO 2 nanoparticles were chosen for investigation, and the protein corona of each type was analyzed using liquid chromatography-tandem mass spectrometry technology. In total, 115 and 48 plasma proteins from the rat were identified as being bound to negatively charged 20 nm and 100 nm SiO 2 nanoparticles, respectively, and 50 and 36 proteins were found for 20 nm and 100 nm arginine-coated SiO 2 nanoparticles, respectively. Higher numbers of proteins were adsorbed onto the 20 nm sized SiO 2 nanoparticles than onto the 100 nm sized nanoparticles regardless of charge. When proteins were compared between the two charges, higher numbers of proteins were found for arginine-coated positively charged SiO 2 nanoparticles than for the negatively charged nanoparticles. The proteins identified as bound in the corona from SiO 2 nanoparticles were further analyzed with ClueGO, a Cytoscape plugin used in protein ontology and for identifying biological interaction pathways. Proteins bound on the surface of nanoparticles may affect functional and conformational properties and distributions in complicated biological processes.

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Implication of oxidative stress in size-dependent toxicity of silica nanoparticles in kidney cells

Cited by 160 publications

References 53 publications

Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

Overendocytosis of gold nanoparticles increases autophagy and apoptosis in hypoxic human renal proximal tubular cells

Size and Cell Type Dependent Uptake of Silica Nanoparticles

Analysis of SiO2 nanoparticles binding proteins in rat blood and brain homogenate

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