Toxicogenomics as an “open” system to detect tissue-specific responses to toxicants: Nanoparticles as a proof of principle in fish (original) (raw)
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Comparative Biochemistry and Physiology Part A: Molecular & Integrative Physiology, 2013
Nanomaterials (NM) industry had grown in the last decade, although there are few studies concerning its potential toxicity effects on aquatic organisms. In this study the freshwater zebrafish (Danio rerio) was exposed to two kinds of carbon NM, single-wall carbon nanotubes (SWCNT) and fullerenol [C 60 (OH) 18-22 (OK 4)] to analyze oxidative stress responses on fish brain. Adult zebrafish (mean mass: 0.52 ± 0.01 g) were submitted to intraperitoneal injections of SWCNT suspension and fullerenol solution (30 mg/kg of fish), receiving one or two doses with a time interval of 24 h. Results showed that total antioxidant capacity was lowered in brains of fish exposed 24 h to fullerenol when compared to those from SWCNT treatment (p b 0.05). After 48 h, fullerenol induced higher expression of both catalytic and regulatory subunits of enzyme glutamate cysteine ligase when compared to control group (p b 0.05), indicating an antioxidant behavior. In vitro assays showed a dual effect of SWCNT, since a pro-oxidant behavior was observed at low concentrations (0.1 and 1.0 mg/L) and an antioxidant one at the highest concentration (10.0 mg/L). Few biological responses were altered by this NM: decrease in total antioxidant capacity and induction of the expression of the transcription factor Nrf2 when compared to control group.
BioMed Research International, 2013
Even though technologies involving nano/microparticles have great potential, it is crucial to determine possible toxicity of these technological products before extensive use. Fullerenes C60are nanomaterials with unique physicochemical and biological properties that are important for the development of many technological applications. The aim of this study was to evaluate the consequences of nonphotoexcited fullerene C60exposure in brain acetylcholinesterase expression and activity, antioxidant responses, and oxidative damage using adult zebrafish as an animal model. None of the doses tested (7.5, 15, and 30 mg/kg) altered AChE activity, antioxidant responses, and oxidative damage when zebrafish were exposed to nonphotoexcited C60nano/microparticles during 6 and 12 hours. However, adult zebrafish exposed to the 30 mg/kg dose for 24 hours have shown enhanced AChE activity and augmented lipid peroxidation (TBARS assays) in brain. In addition, the up-regulation of brain AChE activity w...
Aquatic Toxicology, 2014
Compounds from the nanotechnology industry, such as carbon-based nanomaterials, are strong candidates to contaminate aquatic environments because their production and disposal have exponentially grown in a few years. Previous evidence shows that fullerene C 60 , a carbon nanomaterial, can facilitate the intake of metals or PAHs both in vivo and in vitro, potentially amplifying the deleterious effects of these toxicants in organisms. The present work aimed to investigate the effects of fullerene C 60 in a Danio rerio (zebrafish) hepatocyte cell lineage exposed to benzo[a]pyrene (BaP) in terms of cell viability, oxidative stress parameters and BaP intracellular accumulation. Additionally, a computational docking was performed to investigate the interaction of the fullerene C 60 molecule with the detoxificatory and antioxidant enzyme GST. Fullerene C 60 provoked a significant (p < 0.05) loss in cellular viability when co-exposed with BaP at 0.01, 0.1 and 1.0 g/L, and induced an increase (p < 0.05) in BaP accumulation in the cells after 3 and 4 h of exposure. The levels of reactive oxygen species (ROS) in the cells exposed to BaP were diminished (p < 0.05) by the fullerene addition, and the increase of the GST activity observed in the BaP-only treated cells was reduced to the basal levels by co-exposure to fullerene. However, despite the potential of the fullerene molecule to inhibit GST activity, demonstrated by the computational docking, the nanomaterial did not significantly (p > 0.05) alter the enzyme activity when added to GST purified extracts from the zebrafish hepatocyte cells. These results show that fullerene C 60 can increase the intake of BaP into the cells, decreasing cell viability and impairing the detoxificatory response by phase II enzymes, such as GST, and this latter effect should be occurring at the transcriptional level.
Marine Environmental Research, 2006
Water-soluble fullerene (nC 60) has been shown to induce lipid peroxidation (LPO) in brain of juvenile largemouth bass (LMB, Micropterus salmoides) [Oberdö rster, E., 2004. Manufactured nanomaterials (fullerenes, C 60) induce oxidative stress in brain of juvenile largemouth bass. Environ. Health Persp. 112, 1058-1062]; and upregulate genes related to the inflammatory response and metabolism, most notably CYP2K4 [Oberdö rster, G., Oberdö rster, E., Oberdö rster, J., 2005. Nanotoxicology: an emerging discipline evolving from 116 studies of ultrafine particles. Environ. Health Persp. 113, 823-839]. The initial study in LMB was performed using tetrahydrofuran (THF)-solubilized nC 60 , although C 60 can also be solubilized by stirring in water. The current study investigates differences in acute toxicity to Daphnia magna between THF-solubilized and water-stirred-nC 60 as a range-find for further assays in adult male fathead minnow (FHM, Pimephales promelas). The daphnia 48-h LC 50 for THF-nC 60 was at least one order of magnitude less (0.8 ppm) than that for waterstirred-nC 60 (>35 ppm). FHM were dosed with either 0.5 ppm of THF-or water-stirred-nC 60 for 48 h. There was 100% mortality in the THF-nC 60-exposed fish between 6 and 18 h, while the
Aquatic Toxicology, 2012
In consequence of their growing use and demand, the inevitable environmental presence of nanomaterials (NMs) has raised concerns about their potential deleterious effects to aquatic environments. The carbon NM fullerene (C 60), which forms colloidal aggregates in water, and its water-soluble derivative fullerol (C 60 (OH) 18-22), which possesses antioxidant properties, are known to be photo-excited by ultraviolet (UV) or visible light. To investigate their potential hazards to aquatic organisms upon exposure to UV sunlight, this study analyzed (a) the in vitro behavior of fullerene and fullerol against peroxyl radicals (ROO •) under UV-A radiation and (b) the effects of these photo-excited NMs on oxidative stress parameters in functional gills extracted from the fish Cyprinus carpio (Cyprinidae). The variables measured were the total antioxidant capacity, lipid peroxidation (TBARS), the activities of the antioxidant enzymes glutathione reductase (GR) and glutamate cysteine ligase (GCL), and the levels of the non-enzymatic antioxidant glutathione (GSH). The obtained results revealed the following: (1) both NMs behaved in vitro as antioxidants against ROO • in the dark and as pro-oxidants in presence of UV-A, the latter effect being reversed by the addition of sodium azide, which is a singlet oxygen (1 O 2) quencher; (2) fullerene induced toxicity with or without UV-A incidence, with a significant (p < 0.05) increase in lipid peroxidation (with greater damage under illumination), a decrease in GCL activity, and the depletion of GSH stocks (under illumination), all of which were attributed to 1 O 2 generation; and (3) fullerol also decreased GCL activity and GSH formation (p < 0.05) but without lipid damage. The overall results show that fullerene can be toxic with or without light incidence, whereas UV radiation seems to play a key role in the environmental toxicity of carbon NMs through 1 O 2 formation.
Mutation research, 2012
Whilst there is growing concern over the potential detrimental impact of engineered nanoparticles (ENPs) on the natural environment, little is known about their interactions with other contaminants. In the present study, marine mussels (Mytilus sp.) were exposed for 3 days to C(60) fullerenes (C(60); 0.10-1mgl(-1)) and a model polycyclic aromatic hydrocarbon (PAH), fluoranthene (32-100μgl(-1)), either alone or in combination. The first two experiments were conducted by exposing the organisms to different concentrations of C(60) and fluoranthene alone, in order to determine the effects on total glutathione levels (as a measure of generic oxidative stress), genotoxicity (DNA strand breaks using Comet assay in haemocytes), DNA adduct analyses (using (32)P-postlabelling method) in different organs, histopathological changes in different tissues (i.e. adductor muscle, digestive gland and gills) and physiological effects (feeding or clearance rate). Subsequently, in the third experiment, ...
Intraperitoneal Exposure to Nano/Microparticles of Fullerene (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1">mml:mrowmml:msubmml:mrowmml:mtextCmml:mrowmml:mtext60) Increases Acetylcholines...
BioMed Research International, 2013
Even though technologies involving nano/microparticles have great potential, it is crucial to determine possible toxicity of these technological products before extensive use. Fullerenes C 60 are nanomaterials with unique physicochemical and biological properties that are important for the development of many technological applications. The aim of this study was to evaluate the consequences of nonphotoexcited fullerene C 60 exposure in brain acetylcholinesterase expression and activity, antioxidant responses, and oxidative damage using adult zebrafish as an animal model. None of the doses tested (7.5, 15, and 30 mg/kg) altered AChE activity, antioxidant responses, and oxidative damage when zebrafish were exposed to nonphotoexcited C 60 nano/microparticles during 6 and 12 hours. However, adult zebrafish exposed to the 30 mg/kg dose for 24 hours have shown enhanced AChE activity and augmented lipid peroxidation (TBARS assays) in brain. In addition, the up-regulation of brain AChE activity was neither related to the transcriptional control (RT-qPCR analysis) nor to the direct action of nonphotoexcited C 60 nano/microparticles on the protein (in vitro results) but probably involved a posttranscriptional or posttranslational modulation of this enzymatic activity. Taken together these findings provided further evidence of toxic effects on brain after C 60 exposure.
Environmental Pollution, 2018
This study aimed to assess the toxicological consequences related to the interaction of fullerene nanoparticles (C60) and Benzo(α)pyrene (B(α)P) on zebrafish embryos, which were exposed to C60 and B(α)P alone and to C60 doped with B(α)P. The uptake of pollutants into their tissues and intra-cellular localization were investigated by immunofluorescence and electron microscopy. A set of biomarkers of genotoxicity and oxidative stress, as well as functional proteomics analysis were applied to assess the toxic effects due to C60 interaction with B(α)P. The carrier role of C60 for B(α)P was observed, however adsorption on C60 did not affect the accumulation and localization of B(α)P in the embryos. Instead, C60 doped with B(α)P resulted more prone to sedimentation and less bioavailable for the embryos compared to C60 alone. As for toxicity, our results suggested that C60 alone elicited oxidative stress in embryos and a down-regulation of proteins involved in energetic metabolism. The C60 + B(α)P induced cellular response mechanisms similar to B(α)P alone, but generating greater cellular damages in the exposed embryos.
Environmental Science & Technology, 2009
This study aimed to clarify whether fullerene C 60 nanoparticles induced lipid peroxidation in Cyprinus carpio brains. A stable well-characterized aqueous suspension of C 60 nanoparticle (diameter: 50th and 95th percentiles, 36 and 95 nm respectively) with 0.1% Tween80 solution was prepared by bead milling. Lipid hydroperoxides (LPO) were measured in vitro in homogenized fish brain tissues containing 33 µg/mg-protein dispersed C 60 nanoparticles under light and dark conditions to verify the lipid peroxidation ability of C 60 and the interference of light exposure by using a commercial assay kit. The LPO concentration significantly increased under the light condition but not under the dark condition. This suggests that C 60 has the lipid peroxidation ability under light condition, and the light exposure that occurs during the dissection and preparation of fish brain samples containing C 60 for the LPO assay interferes with the measurements of the in vivo LPO levels. Therefore, dissection and assay in the in vivo experiment were conducted under a yellow lamp or dark condition to avoid the interference of light. Moreover, the result of the in vitro test suggests that the LPO assay with irradiation might be a good method for detecting C 60 in brain tissues. In the in vivo experiment, C. carpio was exposed to 4.5 mg/L nano C 60 suspension for 48 h, following which the brain LPO concentration was measured. In the in vivo experiment, no fish died or exhibited abnormal symptoms during exposure. LPO assay of the C. carpio brain samples confirmed the absence of lipid peroxidation after exposure to 4.5 mg/L aqueous C 60 nanoparticle suspension for 48 h. Additional LPO assay under irradiation showed that C 60 did not reach the brain.