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      Cytotoxicity and oxidative stress induced by different metallic nanoparticles on human kidney cells

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          Abstract

          Background

          Some manufactured nanoparticles are metal-based and have a wide variety of applications in electronic, engineering and medicine. Until now, many studies have described the potential toxicity of NPs on pulmonary target, while little attention has been paid to kidney which is considered to be a secondary target organ. The objective of this study, on human renal culture cells, was to assess the toxicity profile of metallic nanoparticles (TiO 2, ZnO and CdS) usable in industrial production. Comparative studies were conducted, to identify whether particle properties impact cytotoxicity by altering the intracellular oxidative status.

          Results

          Nanoparticles were first characterized by size, surface charge, dispersion and solubility. Cytotoxicity of NPs was then evaluated in IP15 (glomerular mesangial) and HK-2 (epithelial proximal) cell lines. ZnO and CdS NPs significantly increased the cell mortality, in a dose-dependent manner. Cytotoxic effects were correlated with the physicochemical properties of NPs tested and the cell type used. Analysis of reactive oxygen species and intracellular levels of reduced and oxidized glutathione revealed that particles induced stress according to their composition, size and solubility. Protein involved in oxidative stress such as NF-κb was activated with ZnO and CdS nanoparticles. Such effects were not observed with TiO 2 nanoparticles.

          Conclusion

          On glomerular and tubular human renal cells, ZnO and CdS nanoparticles exerted cytotoxic effects that were correlated with metal composition, particle scale and metal solubility. ROS production and oxidative stress induction clearly indicated their nephrotoxic potential.

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          Most cited references52

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          Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues

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            Comparison of the mechanism of toxicity of zinc oxide and cerium oxide nanoparticles based on dissolution and oxidative stress properties.

            Nanomaterials (NM) exhibit novel physicochemical properties that determine their interaction with biological substrates and processes. Three metal oxide nanoparticles that are currently being produced in high tonnage, TiO(2), ZnO, and CeO(2), were synthesized by flame spray pyrolysis process and compared in a mechanistic study to elucidate the physicochemical characteristics that determine cellular uptake, subcellular localization, and toxic effects based on a test paradigm that was originally developed for oxidative stress and cytotoxicity in RAW 264.7 and BEAS-2B cell lines. ZnO induced toxicity in both cells, leading to the generation of reactive oxygen species (ROS), oxidant injury, excitation of inflammation, and cell death. Using ICP-MS and fluorescent-labeled ZnO, it is found that ZnO dissolution could happen in culture medium and endosomes. Nondissolved ZnO nanoparticles enter caveolae in BEAS-2B but enter lysosomes in RAW 264.7 cells in which smaller particle remnants dissolve. In contrast, fluorescent-labeled CeO(2) nanoparticles were taken up intact into caveolin-1 and LAMP-1 positive endosomal compartments, respectively, in BEAS-2B and RAW 264.7 cells, without inflammation or cytotoxicity. Instead, CeO(2) suppressed ROS production and induced cellular resistance to an exogenous source of oxidative stress. Fluorescent-labeled TiO(2) was processed by the same uptake pathways as CeO(2) but did not elicit any adverse or protective effects. These results demonstrate that metal oxide nanoparticles induce a range of biological responses that vary from cytotoxic to cytoprotective and can only be properly understood by using a tiered test strategy such as we developed for oxidative stress and adapted to study other aspects of nanoparticle toxicity.
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              The potential environmental impact of engineered nanomaterials.

              With the increased presence of nanomaterials in commercial products, a growing public debate is emerging on whether the environmental and social costs of nanotechnology outweigh its many benefits. To date, few studies have investigated the toxicological and environmental effects of direct and indirect exposure to nanomaterials and no clear guidelines exist to quantify these effects.
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                Author and article information

                Journal
                Part Fibre Toxicol
                Particle and Fibre Toxicology
                BioMed Central
                1743-8977
                2011
                3 March 2011
                : 8
                : 10
                Affiliations
                [1 ]Laboratoire Biologie Cellulaire, FRE CNRS 3396 Université Bordeaux Segalen, 146 rue Léo-Saignat, 33076 Bordeaux Cedex, France
                [2 ]INSERM 1026, Bioingénierie tissulaire BioTis, Université Bordeaux Segalen, 146 rue Léo-Saignat, 33076 Bordeaux Cedex, France
                [3 ]CNRS Université de Bordeaux, ICMCB, 87 avenue du Dr Schweitzer, 33608 Pessac Cedex, France
                [4 ]Laboratoire Hydrologie-Environnement, UFR Sciences Pharmaceutiques, Université Bordeaux Segalen, 146 rue Léo-Saignat, 33 076 Bordeaux Cedex, France
                Article
                1743-8977-8-10
                10.1186/1743-8977-8-10
                3058043
                21371295
                cbec44ac-074d-4dc4-8035-b8c59e5b5b18
                Copyright ©2011 Pujalté et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 November 2010
                : 3 March 2011
                Categories
                Research

                Toxicology
                Toxicology

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