Cytotoxicity Effects of Graphene and Single-Wall Carbon Nanotubes in Neural Phaeochromocytoma-Derived PC12 Cells

Neurochemistry Laboratory, Division of Neurotoxicology, National Center for Toxicological Research, Food and Drug Administration, 3900 NCTR Road, Jefferson, Arkansas 72079, USA.
ACS Nano (Impact Factor: 12.88). 06/2010; 4(6):3181-6. DOI: 10.1021/nn1007176
Source: PubMed

ABSTRACT Graphitic nanomaterials such as graphene layers (G) and single-wall carbon nanotubes (SWCNT) are potential candidates in a large number of biomedical applications. However, little is known about the effects of these nanomaterials on biological systems. Here we show that the shape of these materials is directly related to their induced cellular toxicity. Both G and SWCNT induce cytotoxic effects, and these effects are concentration- and shape-dependent. Interestingly, at low concentrations, G induced stronger metabolic activity than SWCNT, a trend that reversed at higher concentrations. Lactate dehydrogenase levels were found to be significantly higher for SWCNT as compared to the G samples. Moreover, reactive oxygen species were generated in a concentration- and time-dependent manner after exposure to G, indicating an oxidative stress mechanism. Furthermore, time-dependent caspase 3 activation after exposure to G (10 microg/mL) shows evidence of apoptosis. Altogether these studies suggest different biological activities of the graphitic nanomaterials, with the shape playing a primary role.

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    • "A number of studies performed with CNTs have evaluated their toxicity to different organs, such as the lungs, kidneys, and liver (Awasthi et al., 2013; Deng et al., 2009; Li et al., 2007). Several in vitro studies have confirmed that CNTs could generate neurotoxic effects, including decreasing cell activity (Belyanskaya et al., 2009; Zhang et al., 2010). In addition, our previous studies have showed that MWCNTs induce cytotoxicity in C6 cells (Han et al., 2012) and inhibit CA1 glutamatergic synaptic transmission in rat hippocampal slices in vitro (Chen et al., 2014). "
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    ABSTRACT: Multi-walled carbon nanotubes (MWCNTs) have shown potential applications in many fields, especially in the field of biomedicine. Several studies have reported that MWCNTs induce apoptosis and oxidative damage in nerve cells during in vitro experiments. However, there are few studies focused on the neurotoxicity of MWCNTs used in vivo. Many studies have reported that autophagy, a cellular stress response to degrade damaged cell components, can be activated by diverse nanoparticles. In this study, we investigated the neurotoxic effects of MWCNTs on hippocampal synaptic plasticity and spatial cognition in rats. Then, we used an inhibitor of autophagy called chloroquine (CQ) to examine whether autophagy plays an important role in hippocampal synaptic plasticity, since this was damaged by MWCNTs. In this study, adult male Wister rats were randomly divided into three groups: a control group, a group treated with MWCNTs (2.5mg/kg/day) and a group treated with MWCNTs+CQ (20mg/kg/day). After two-weeks of intraperitoneal (i.p.) injections, rats were subjected to the Morris water maze (MWM) test, and the long-term potentiation (LTP) and other biochemical parameters were determined. Results showed that MWCNTs could induce cognitive deficits, histopathological alteration and changes of autophagy level (increased the ratio of LC3 II /LC3 I and the expression of Beclin-1). Furthermore, we found that CQ could suppress MWCNTs-induced autophagic flux and partly rescue the synapse deficits, which occurred with the down-regulation of NR2B (a subunit of NMDA receptor) and synaptophysin (SYP) in the hippocampus. Our results suggest that MWCNTs could induce cognitive deficits in vivo via the increased autophagic levels, and provide a potential strategy to avoid the adverse effects of MWCNTs. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Toxicology 08/2015; DOI:10.1016/j.tox.2015.08.011 · 3.62 Impact Factor
    • "In parallel to efforts directed at identifying new applications for carbon nanotubes (CNTs) and at improving ways to mass-produce them [1] [2], efforts are underway to examine health and ecological effects of these materials, as increasing production and use certainly will lead to release to the environment and biological exposure [3] [4] [5]. Of the several proposed processes used to explain toxicity of these materials, ''oxidative stress'' is recognized as one of the likely causes [6] [7] [8] [9] [10]. Oxidative stress presumably occurs through reactive oxygen species (ROS) generation, and while mechanisms of photo-induced ROS generation by CNTs has been reported [11] [12] [13], there is limited information on light-independent generation of ROS and the underlying mechanisms responsible for this generation [14]. "
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    ABSTRACT: Although induction of oxidative stress is widely accepted as one of the major cytotoxic effects of carbon nanotubes (CNTs), there is no solid understanding of how biological redox reactions are affected and how reactive oxygen species (ROS) are generated by CNTs, especially when they are coated with various dispersing agents. In this study, we investigated electron transfer from biological reducing agents through nonfunctionalized single-walled carbon nanotubes (SWCNTs) to molecular oxygen, generating ROS in the process. Electron transfer rates in the colloidal SWCNT suspensions depended on the dispersant used to stabilize them, with six dispersants examined. Oxidation of both nicotinamide adenine dinucleotide (NADH) and dithiothreitol was catalyzed by SWCNTs coated with either cetyltrimethylammonium bromide (CTAB) or Suwannee River natural organic matter (SRNOM). SWCNTs coated with other types of surfactants showed only slight effect. In the presence of NADH or dithiothreitol, generation of ROS also was dispersant-dependent, with CTAB- and SRNOM-coated SWCNTs generating significant amounts of superoxide anion and hydrogen peroxide. In systems containing xanthine and xanthine oxidase, accumulated charge on the SWCNTs appeared to be transferred to superoxide anion, resulting in indirect disproportionation of superoxide anion, forming more hydrogen peroxide.
    Carbon 08/2015; 89:361-371. DOI:10.1016/j.carbon.2015.03.052 · 6.20 Impact Factor
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    • "However, in this type of toxicity, the key role is played by factors such as the duration of the culture and the graphene structure defined as the number of layers, shape, texture and its dimensions. [5] [8] It has been found that the most crucial factors that play an important role in the cell culture are the changes in the hydrophilic/hydrophobic nature of the substrate and its roughness.[7,9À11] With regard to the cytotoxic effects, what is of particular importance is the purity of the substrate, which is fundamentally different in products obtained from carbon *Corresponding author. "
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    ABSTRACT: In tissue engineering, the possibility of a comprehensive restoration of the tissue, structure or a portion of the organ is largely determined by the type of material used. A wide range of materials such as graphene and other carbon nanocompounds which have different physical and chemical properties can be expected to react differently upon contact with biomolecules, cells and tissues. This mini-review describes the current knowledge on biocompatibility of graphene and its derivatives with a variety of mammalian cells, such as osteoblasts, neuroendocrine cells, fibroblasts NIH/3T3 line, PMEFs (primary mouse embryonic fibroblasts), stem cells and neurons. The results from different studies give hope for the possibility of graphene to be used in the regeneration of almost all tissues, including neural tissue implants or in the form of neural chips, which may allow in the future treatment of degenerative diseases and injuries of the central nervous system.
    Biotechnology & Biotechnological Equipment 02/2015; 29(3). DOI:10.1080/13102818.2015.1009726 · 0.30 Impact Factor
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