RESUMO
Quantum dots exhibit extraordinary optical and mechanical properties, and the number of their applications is increasing. In order to investigate a possible effect of coating on the inhalation toxicity of previously tested non-coated CdS/Cd(OH)2 quantum dots and translocation of these very small particles from the lungs, rats were exposed to coated quantum dots or CdCl2 aerosol (since Cd(2+) was present as impurity), 6h/d for 5 consecutive days. Cd content was determined in organs and excreta after the end of exposure and three weeks thereafter. Toxicity was determined by examination of broncho-alveolar lavage fluid and microscopic evaluation of the entire respiratory tract. There was no evidence for translocation of particles from the respiratory tract. Evidence of a minimal inflammatory process was observed by examination of broncho-alveolar lavage fluid. Microscopically, minimal to mild epithelial alteration was seen in the larynx. The effects observed with coated quantum dots, non-coated quantum dots and CdCl2 were comparable, indicating that quantum dots elicited no significant effects beyond the toxicity of the Cd(2+) ion itself. Compared to other compounds with larger particle size tested at similarly low concentrations, quantum dots caused much less pronounced toxicological effects. Therefore, the present data show that small particle sizes with corresponding high surfaces are not the only factor triggering the toxic response or translocation.
Assuntos
Compostos de Cádmio/toxicidade , Glutaral/toxicidade , Hidróxidos/toxicidade , Pontos Quânticos/toxicidade , Sistema Respiratório/efeitos dos fármacos , Sulfetos/toxicidade , Aerossóis , Animais , Líquido da Lavagem Broncoalveolar , Cloreto de Cádmio/toxicidade , Compostos de Cádmio/metabolismo , Compostos de Cádmio/urina , Fezes/química , Glutaral/metabolismo , Glutaral/urina , Hidróxidos/metabolismo , Hidróxidos/urina , Exposição por Inalação , Masculino , Tamanho da Partícula , Pontos Quânticos/metabolismo , Ratos , Ratos Wistar , Sistema Respiratório/metabolismo , Sistema Respiratório/patologia , Sulfetos/metabolismo , Sulfetos/urina , Fatores de Tempo , Distribuição Tecidual , Testes de Toxicidade AgudaRESUMO
BACKGROUND: Semiconductor Quantum dots (QDs) have become quite popular thanks to their properties and wide use in biological and biomedical studies. However, these same properties entail new challenges in understanding, predicting, and managing potential adverse health effects following exposure. Cadmium and selenium, which are the major components of the majority of quantum dots, are known to be acutely and chronically toxic to cells and organisms. Protecting the core of nanoparticles can, to some degree, control the toxicity related to cadmium and selenium leakage. RESULTS: This study successfully synthesized and characterized maltodextrin coated cadmium sulfide semiconductor nanoparticles. The results show that CdS-MD nanoparticles are cytotoxic and embryotoxic. CdS-MD nanoparticles in low concentrations (4.92 and 6.56 nM) lightly increased the number of HepG2 cell. A reduction in MDA-MB-231 cells was observed with concentrations higher than 4.92 nM in a dose response manner, while Caco-2 cells showed an important increase starting at 1.64 nM. CdS-MD nanoparticles induced cell death by apoptosis and necrosis in MDA-MD-231 cells starting at 8.20 nM concentrations in a dose response manner. The exposure of these cells to 11.48-14.76 nM of CdS-MD nanoparticles induced ROS production. The analysis of cell proliferation in MDA-MB-231 showed different effects. Low concentrations (1.64 nM) increased cell proliferation (6%) at 7 days (p < 0.05). However, higher concentrations (>4.92 nM) increased cell proliferation in a dose response manner (15-30%) at 7 days. Exposures of chicken embryos to CdS-MD nanoparticles resulted in a dose-dependent increase in anomalies that, starting at 9.84 nM, centered on the heart, central nervous system, placodes, neural tube and somites. No toxic alterations were observed with concentrations of < 3.28 nM, neither in cells nor chicken embryos. CONCLUSIONS: Our results indicate that CdS-MD nanoparticles induce cell death and alter cell proliferation in human cell lines at concentrations higher than 4.92 nM. We also demonstrated that they are embryotoxic. However, no toxic effects were observed with doses lower than 3.28 nM in neither cells nor chicken embryos. The CdS-MD nanoparticles used in this study can be potentially used in bio-imaging applications. However, further studies using mammalian species are required in order to discard more toxic effects.
Assuntos
Compostos de Cádmio/química , Compostos de Cádmio/toxicidade , Polissacarídeos/química , Polissacarídeos/toxicidade , Pontos Quânticos , Sulfetos/química , Sulfetos/toxicidade , Anormalidades Induzidas por Medicamentos/etiologia , Animais , Apoptose/efeitos dos fármacos , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Embrião de Galinha , Desenvolvimento Embrionário/efeitos dos fármacos , Células Hep G2 , Humanos , Estresse Oxidativo/efeitos dos fármacosRESUMO
Semiconductor nanoparticles, such as quantum dots (QDs), were used to carry out experiments in vivo and ex vivo with Trypanosoma cruzi. However, questions have been raised regarding the nanotoxicity of QDs in living cells, microorganisms, tissues and whole animals. The objective of this paper was to conduct a QD nanotoxicity study on living T. cruzi protozoa using analytical methods. This was accomplished using in vitro experiments to test the interference of the QDs on parasite development, morphology and viability. Our results show that after 72 h, a 200 µM cadmium telluride (CdTe) QD solution induced important morphological alterations in T. cruzi, such as DNA damage, plasma membrane blebbing and mitochondrial swelling. Flow cytometry assays showed no damage to the plasma membrane when incubated with 200 µM CdTe QDs for up to 72 h (propidium iodide cells), giving no evidence of classical necrosis. Parasites incubated with 2 µM CdTe QDs still proliferated after seven days. In summary, a low concentration of CdTe QDs (2 µM) is optimal for bioimaging, whereas a high concentration (200 µM CdTe) could be toxic to cells. Taken together, our data indicate that 2 µM QD can be used for the successful long-term study of the parasite-vector interaction in real time.
Assuntos
Compostos de Cádmio/toxicidade , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Pontos Quânticos , Telúrio/toxicidade , Trypanosoma cruzi/efeitos dos fármacos , Animais , Membrana Celular/efeitos dos fármacos , Citometria de Fluxo , Corantes Fluorescentes , Camundongos , Microscopia Eletrônica de Transmissão , Dilatação Mitocondrial , Trypanosoma cruzi/ultraestruturaRESUMO
Semiconductor nanoparticles, such as quantum dots (QDs), were used to carry out experiments in vivo and ex vivo with Trypanosoma cruzi. However, questions have been raised regarding the nanotoxicity of QDs in living cells, microorganisms, tissues and whole animals. The objective of this paper was to conduct a QD nanotoxicity study on living T. cruzi protozoa using analytical methods. This was accomplished using in vitro experiments to test the interference of the QDs on parasite development, morphology and viability. Our results show that after 72 h, a 200 μM cadmium telluride (CdTe) QD solution induced important morphological alterations in T. cruzi, such as DNA damage, plasma membrane blebbing and mitochondrial swelling. Flow cytometry assays showed no damage to the plasma membrane when incubated with 200 μM CdTe QDs for up to 72 h (propidium iodide cells), giving no evidence of classical necrosis. Parasites incubated with 2 μM CdTe QDs still proliferated after seven days. In summary, a low concentration of CdTe QDs (2 μM) is optimal for bioimaging, whereas a high concentration (200 μM CdTe) could be toxic to cells. Taken together, our data indicate that 2 μM QD can be used for the successful long-term study of the parasite-vector interaction in real time.
Assuntos
Animais , Camundongos , Compostos de Cádmio/toxicidade , Proliferação de Células , Dano ao DNA , Pontos Quânticos , Telúrio/toxicidade , Trypanosoma cruzi , Membrana Celular , Citometria de Fluxo , Corantes Fluorescentes , Microscopia Eletrônica de Transmissão , Dilatação Mitocondrial , Trypanosoma cruzi/ultraestruturaRESUMO
Cadmium is a toxicant with known carcinogenic and endocrine disruptor effects. We have previously reported that prenatal exposure to cadmium may induce low birth weight which is associated to increased foetal exposure to glucocorticoids; both signals constitute "hallmarks" of developmental programming. Since the effect of cadmium on the glucocorticoid system of placental carcinogenic cells is unknown, in the present work, we studied the effect of acute low dose of cadmium on cortisol production and 11beta-HSD2 expression and activity by cultured human choriocarcinoma cells (JEG-3). In addition, it was also evaluated whether those effects were related to the methylation index of the HSD11B2 gene, which can be regulated by epigenetic mechanisms. Cells were incubated with low cadmium dose (0.5 and 1 microM) for 24h and viability (MTT), cortisol production (EIA), 11beta-HSD2 expression (qRT-PCR) and activity (radioassay), and methylation index of the HSD11B2 gene were determined. Results show lower cortisol concentrations in the incubation media of exposed cells, which were associated to increased 11beta-HSD2 expression and activity and to a lower methylation index of the gene. These results suggest that cadmium-induced endocrine disruptor effects on JEG-3 cells could be mediated by changes in the methylation status of some target genes.
Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 2/metabolismo , Compostos de Cádmio/toxicidade , Coriocarcinoma/tratamento farmacológico , Poluentes Ambientais/toxicidade , Hidrocortisona/metabolismo , 11-beta-Hidroxiesteroide Desidrogenase Tipo 2/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Coriocarcinoma/metabolismo , Metilação de DNA/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Humanos , RNA Mensageiro/metabolismoRESUMO
Crassostrea virginica is an epibentic filter-feeding bivalve of economical importance in coastal lagoons of the Gulf of Mexico, locations with increasing inputs of heavy metals such as cadmium that have become environmental stressors. In this study, feeding and assimilation of the species were evaluated as physiological indicators of cadmium exposure. For this purpose, the filtration rate (FR), food assimilation (A) and assimilation efficiency (AE) of oysters from the Mandinga Lagoon, Veracruz, Mexico, were examined under sublethal and environmentally realistic cadmium concentrations (95 and 170 micro gCd L(-1)). Semi-static, 12-day bioassays were conducted with organisms placed into individual chambers and fed daily with Tetraselmis suecica. FR was calculated by measuring the depletion in algal density. Caloric contents of food and feces produced were also obtained. Condition Index (CI) and morphometric parameters were evaluated at the beginning and at the end of the assay. Total cadmium concentrations were quantified in water and tissue, and the metal bioconcentration factor (BCF) was calculated. Cadmium exposure significantly reduced FR in oysters (mean value: 0.64 L h(-1) and 0.44 L h(-1)) from control values (1.17 L h(-1)). Extreme values among results demonstrate the existence of a high FR (over 4 L h(-1)) mainly in control oysters, and this was associated with a better physiological condition; a low FR (under 2.5 L h(-1)) indicated metabolic stress as a consequence of Cd exposure. A and AE were significantly modified due to cadmium external levels, and time of exposure. FR and A were linearly related, and both decreased as metal BCF increased. Cadmium bioaccumulation was linearly related with external metal levels. The physiological deterioration of native C. virginica from Mandinga Lagoon was reflected in the alteration of FR, A and AE due to cadmium exposure in concentrations considered sublethal, lowering the feeding and assimilation capability of the organisms. The weight loss and mortality recorded in the oysters exposed to the highest metal concentration, was the final consequence of the overall adverse effect of cadmium exposure.
Assuntos
Compostos de Cádmio/toxicidade , Clorófitas/efeitos dos fármacos , Crassostrea/efeitos dos fármacos , Cadeia Alimentar , Frutos do Mar , Poluentes Químicos da Água/toxicidade , Animais , Bioensaio , Peso Corporal/efeitos dos fármacos , Compostos de Cádmio/análise , Clorófitas/metabolismo , Crassostrea/metabolismo , Monitoramento Ambiental , Longevidade/efeitos dos fármacos , México , Estações do Ano , Testes de Toxicidade , Poluentes Químicos da Água/análiseRESUMO
Cadmium is a strong mutagen that acts by inhibiting DNA mismatch repair, while its toxic effect seems to be related to an indirect oxidative stress that involves glutathione (GSH) mobilization. Among the roles of GSH is the protection of proteins against oxidative damage, by forming reversible mixed disulfides with cysteine residues, a process known as protein glutathionylation and catalyzed by glutaredoxins (Grx). In this current study, Saccharomyces cerevisiae cells deficient in GRX2, growing in 80 muM CdSO(4), showed high mitochondrial mutagenic rate, determined by frequency of mutants that had lost mitochondrial function (petite mutants), high tolerance and lower apoptosis induction. The mutant strain also showed decreased levels of glutathionylated-protein after cadmium exposure, which might difficult the signaling to apoptosis, leading to increased mutagenic rates. Taken together, these results suggest that Grx2 is involved with the apoptotic death induced by cadmium, a form of cellular suicide that might lead of removal of mutated cells.
Assuntos
Apoptose/genética , Compostos de Cádmio/toxicidade , Glutarredoxinas/fisiologia , Mutagênicos/toxicidade , Proteínas de Saccharomyces cerevisiae/fisiologia , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/fisiologia , Sulfatos/toxicidade , Glutarredoxinas/genética , Glutationa/metabolismo , Oxirredução , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Transdução de SinaisRESUMO
In the yeast Saccharomyces cerevisiae, gamma-glutamyl transferase (gamma-GT; EC 2.3.2.2) is a vacuolar-membrane bound enzyme. In this work we verified that S. cerevisiae cells deficient in gamma-GT absorbed almost 2.5-fold as much cadmium as the wild-type (wt) cells, suggesting that this enzyme might be responsible for the recycle of cadmium-glutathione complex stored in the vacuole. The mutant strain showed difficulty in keeping constant levels of glutathione (GSH) during the stress, although the GSH-reductase activity was practically the same in both wt and mutant strains, before and after metal stress. This difficulty to maintain the GSH levels in the gamma-GT mutant strain led to high levels of lipid peroxidation and carbonyl proteins in response to cadmium, higher than in the wt, but lower than in a mutant deficient in GSH synthesis. Although the increased levels of oxidative stress, gamma-GT mutant strain showed to be tolerant to cadmium and showed similar mutation rates to the wt, indicating that the compartmentation of the GSH-cadmium complex in vacuole protects cells against the mutagenic action of the metal. Confirming this hypothesis, a mutant strain deficient in Ycf1, which present high concentrations of GSH-cadmium in cytoplasm due to its deficiency in transport the complex to vacuole, showed increased mutation rates.
Assuntos
Compostos de Cádmio/toxicidade , Glutationa/metabolismo , Mutagênicos/toxicidade , Mutação , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Sulfatos/toxicidade , Vacúolos/metabolismo , gama-Glutamiltransferase/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Compostos de Cádmio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Regulação Fúngica da Expressão Gênica , Glutationa Redutase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Mutagênicos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Sulfatos/metabolismo , Vacúolos/enzimologia , gama-Glutamiltransferase/deficiência , gama-Glutamiltransferase/genéticaRESUMO
Cadmium (Cd) is a toxic heavy metal of continuing occupational and environmental concern with a wide variety of adverse effects. Several studies have shown that cadmium produces DNA strand breaks, DNA-protein cross-links, oxidative DNA damage, chromosomal aberrations, dysregulation of gene expression resulting in enhanced proliferation, depressed apoptosis and/or altered DNA repair. This study was undertaken to investigate the ability of cadmium chloride (CdCl(2)) and cadmium sulphate (CdSO(4)) to induce point mutations in codon 12 of the K-ras protooncogene assessed by polymerase chain reaction-single strand conformation polymorphisms (PCR-SSCP) and RFLP-enriched PCR methods. Also their genotoxic effects were analyzed by the comet assay and sister chromatid exchanges test. The human lung fibroblast cell line MRC-5 was used for the experiments. Sister chromatid exchanges assay (SCEs) frequencies were significantly increased in cells exposed to cadmium salts in relation to controls (p<0.001). Despite the slow increment observed in the three comet parameters considered when cells were treated with cadmium chloride, significant differences between groups were only found in the variable comet moment (CM) (p<0.005). On the other hand, when cells were exposed to cadmium sulphate, the Kruskal-Wallis test showed highly significant differences between groups for migration, tail moment and comet moment parameters (p<0.001). Nevertheless, a null or weak point mutation induction in K-ras protooncogene was detected using polymerase chain reaction-low ionic strength-single strand conformation polymorphisms (PCR-LIS-SSCP) and RFLP-enriched PCR methods when cells were treated with cadmium salts. Thus, inorganic cadmium produces genotoxicity in human lung fibroblast MRC-5 cells, in the absence of significant point mutation of the K-ras gene.
Assuntos
Cloreto de Cádmio/toxicidade , Compostos de Cádmio/toxicidade , Dano ao DNA , Genes ras/genética , Mutação Puntual/genética , Sulfatos/toxicidade , Linhagem Celular , Ensaio Cometa , Genes ras/efeitos dos fármacos , Humanos , Polimorfismo de Fragmento de Restrição , Polimorfismo Conformacional de Fita Simples , Troca de Cromátide Irmã/efeitos dos fármacos , Estatísticas não ParamétricasRESUMO
Human exposure to metals is frequent due to their ubiquity, wide use in industry, and environmental persistence. Direct and indirect genotoxic effects of cadmium (Cd) and arsenic (As) were reported. However, the mechanisms of induction of genetic damage are not well known. The aim of the present work was to evaluate the degree of damage induced by Cd and As salts in a human lung fibroblasts cell line using the single cell gel electrophoresis assay (SCGE). MRC-5 cells were treated with cadmium chloride (CdCl(2)), cadmium sulfate (CdSO(4)), sodium arsenite (NaAsO(2)) and cacodylic acid (C(2)H(7)AsO(2)). A significant dose-dependent increment in the extent of DNA migration as well as in the percentage of cells with tails was observed (P<0.001) after treatment with CdSO(4) and NaAsO(2). Treatment with CdCl(2) induced a relatively low level of DNA strand breaks in comparison with that induced by CdSO(4). The increase migration observed with the three compounds could be originated either by the direct induction of DNA lesions or by the inhibition of excision repair mechanisms. On the other hand, cells treated with C(2)H(7)AsO(2) showed a decrease in the migration length with the three doses employed (P<0.001). The decrease in the rate of DNA migration could be a consequence of the induction of DNA cross-links by organic arsenicals.Cd and As salts induced DNA damage in fibroblast cells, detected as DNA migration in the single cell gel (SCG) assay. The distribution of DNA migration among cells as a function of dose revealed that the majority of exposed cells showed more DNA damage than cells obtained from control cultures. The potential for human exposure to both metals has been increased over the years due to the increment in their use. For this reason, elucidation of carcinogenic mechanisms is very important.