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1.
J Toxicol Sci ; 46(9): 425-435, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34470994

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 enters host cells by binding with the receptor angiotensin-converting enzyme 2 (ACE2). While ACE2 is expressed in multiple cell types, it has been implicated in the clinical progression of COVID-19 as an entry point for SARS-CoV-2 into respiratory cells. Human respiratory cells, such as airway and alveolar epithelial type II (ATII) cells, are considered essential for COVID-19 research; however, primary human respiratory cells are difficult to obtain. In the present study, we generated ATII and club cells from human induced pluripotent stem cells (hiPSCs) for SARS-CoV-2 infection and drug testing. The differentiated cells expressed ATII markers (SFTPB, SFTPC, ABCA3, SLC34A2) or club cell markers (SCGB1A1 and SCGB3A2). Differentiated cells, which express ACE2 and TMPRSS2, were infected with SARS-CoV-2. Remdesivir treatment decreased intracellular SARS-CoV-2 viral replication and, furthermore, treatment with bleomycin showed cytotoxicity in a concentration-dependent manner. These data suggest that hiPSC-derived AT2 and club cells provide a useful in vitro model for drug development.


Assuntos
Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Células Epiteliais Alveolares/efeitos dos fármacos , Antivirais/farmacologia , Bleomicina/toxicidade , Diferenciação Celular , Células-Tronco Pluripotentes Induzidas/efeitos dos fármacos , SARS-CoV-2/efeitos dos fármacos , Testes de Toxicidade , Monofosfato de Adenosina/farmacologia , Alanina/farmacologia , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Células Epiteliais Alveolares/virologia , COVID-19/tratamento farmacológico , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Interações Hospedeiro-Patógeno , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Células-Tronco Pluripotentes Induzidas/patologia , Células-Tronco Pluripotentes Induzidas/virologia , Fenótipo , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/patogenicidade , Replicação Viral/efeitos dos fármacos
2.
Artigo em Inglês | MEDLINE | ID: mdl-34444108

RESUMO

Antiretroviral drugs for the treatment of human immunodeficiency virus (HIV) and other viral infections are among the emerging contaminants considered for ecological risk assessment. These compounds have been reported to be widely distributed in water bodies and other aquatic environments, while data concerning the risk they may pose to unintended non-target species in a different ecosystem (environment) is scanty. In South Africa and other developing countries, lamivudine is one of the common antiretrovirals applied. Despite this, little is known about its environmental impacts as an emerging contaminant. The present study employed a battery of ecotoxicity bioassays to assess the environmental threat lamivudine poses to aquatic fauna and flora. Daphnia magna (filter feeders), the Ames bacterial mutagenicity test, Lactuca sativa (lettuce) germination test, and the Allium cepa root tip assay were conducted, testing lamivudine at two concentrations (10 and 100 µg/L), with environmental relevance. The Daphnia magna toxicity test revealed a statistically significant response (p << 0.05) with a mortality rate of 85% on exposure to 100 µg/L lamivudine in freshwater, which increased to 100% at 48-h exposure. At lower concentrations of 10 µg/L lamivudine, 90% and 55% survival rates were observed at 24 h and 48 h, respectively. No potential mutagenic effects were observed from the Ames test at both concentrations of lamivudine. Allium cepa bioassays revealed a noticeable adverse impact on the root lengths on exposure to 100 µg/L lamivudine. This impact was further investigated through microscopic examination, revealing some chromosomal aberration in the exposed Allium cepa root tips. The Lactuca sativa bioassay showed a slight adverse impact on both the germination rate of the seeds and their respective hypocotyl lengths compared to the control. Overall, this indicates that lamivudine poses an ecological health risk at different trophic levels, to both flora and fauna, at concentrations previously found in the environment.


Assuntos
Ecossistema , Poluentes Químicos da Água , Animais , Daphnia , Humanos , Lamivudina/toxicidade , Cebolas , Testes de Toxicidade , Poluentes Químicos da Água/toxicidade
3.
Int J Mol Sci ; 22(15)2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34360696

RESUMO

Neurodevelopment is uniquely sensitive to toxic insults and there are concerns that environmental chemicals are contributing to widespread subclinical developmental neurotoxicity (DNT). Increased DNT evaluation is needed due to the lack of such information for most chemicals in common use, but in vivo studies recommended in regulatory guidelines are not practical for the large-scale screening of potential DNT chemicals. It is widely acknowledged that developmental neurotoxicity is a consequence of disruptions to basic processes in neurodevelopment and that testing strategies using human cell-based in vitro systems that mimic these processes could aid in prioritizing chemicals with DNT potential. Myelination is a fundamental process in neurodevelopment that should be included in a DNT testing strategy, but there are very few in vitro models of myelination. Thus, there is a need to establish an in vitro myelination assay for DNT. Here, we summarize the routes of myelin toxicity and the known models to study this particular endpoint.


Assuntos
Encéfalo/fisiopatologia , Modelos Biológicos , Bainha de Mielina , Transtornos do Neurodesenvolvimento/etiologia , Síndromes Neurotóxicas/etiologia , Oligodendroglia , Animais , Humanos , Transtornos do Neurodesenvolvimento/induzido quimicamente , Transtornos do Neurodesenvolvimento/fisiopatologia , Síndromes Neurotóxicas/fisiopatologia , Organoides , Testes de Toxicidade
4.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360880

RESUMO

To prevent congenital defects arising from maternal exposure, safety regulations require pre-market developmental toxicity screens for industrial chemicals and pharmaceuticals. Traditional embryotoxicity approaches depend heavily on the use of low-throughput animal models which may not adequately predict human risk. The validated embryonic stem cell test (EST) developed in murine embryonic stem cells addressed the former problem over 15 years ago. Here, we present a proof-of-concept study to address the latter challenge by updating all three endpoints of the classic mouse EST with endpoints derived from human induced pluripotent stem cells (hiPSCs) and human fibroblasts. Exposure of hiPSCs to selected test chemicals inhibited differentiation at lower concentrations than observed in the mouse EST. The hiPSC-EST also discerned adverse developmental outcomes driven by novel environmental toxicants. Evaluation of the early cardiac gene TBX5 yielded similar toxicity patterns as the full-length hiPSC-EST. Together, these findings support the further development of hiPSCs and early molecular endpoints as a biologically relevant embryotoxicity screening approach for individual chemicals and mixtures.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Fluoruracila/toxicidade , Células-Tronco Pluripotentes Induzidas/citologia , Miócitos Cardíacos/citologia , Penicilina G/farmacologia , Teratógenos/farmacologia , Testes de Toxicidade/métodos , Tretinoína/toxicidade , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Anormalidades Congênitas/prevenção & controle , Desenvolvimento Embrionário/efeitos dos fármacos , Fibroblastos/citologia , Humanos , Camundongos , Células-Tronco Embrionárias Murinas/citologia , Miócitos Cardíacos/efeitos dos fármacos , Proteínas com Domínio T
5.
Chem Biol Interact ; 347: 109618, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34364836

RESUMO

The toxicity of hybrid nanoparticles, consisting of non-toxic components, zirconium dioxide nanoparticles (ZrO2 NPs), and caffeic acid (CA), was examined against four different cell lines (HTR-8 SV/Neo, JEG-3, JAR, and HeLa). Stable aqueous ZrO2 sol, synthesized by forced hydrolysis, consists of 3-4 nm in size primary particles organized in 30-60 nm in size snowflake-like particles, as determined by transmission electron microscopy and direct light scattering measurements. The surface modification of ZrO2 NPs with CA leads to the formation of an interfacial charge transfer (ICT) complex followed by the appearance of absorption in the visible spectral range. The spectroscopic observations are complemented with the density functional theory calculations using a cluster model. The ZrO2 NPs and CA are non-toxic against four different cell lines in investigated concentration range. Also, ZrO2 NPs promote the proliferation of HTR-8 SV/Neo, JAR, and HeLa cells. On the other hand, hybrid ZrO2/CA NPs induced a significant reduction of the viability of the JEG-3 cells (39 %) for the high concentration of components (1.6 mM ZrO2 and 0.4 mM CA).


Assuntos
Ácidos Cafeicos/toxicidade , Nanopartículas Metálicas/toxicidade , Placenta/efeitos dos fármacos , Zircônio/toxicidade , Ácidos Cafeicos/química , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Teoria da Densidade Funcional , Feminino , Humanos , Nanopartículas Metálicas/química , Modelos Químicos , Tamanho da Partícula , Placenta/patologia , Gravidez , Testes de Toxicidade , Zircônio/química
6.
Molecules ; 26(16)2021 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-34443693

RESUMO

The multi-step synthesis, physico-chemical characterization, and biological activity of novel valine-derived compounds, i.e., N-acyl-α-amino acids, 1,3-oxazol-5(4H)-ones, N-acyl-α-amino ketones, and 1,3-oxazoles derivatives, bearing a 4-[(4-chlorophenyl)sulfonyl]phenyl moiety are reported here. The structures of the newly synthesized compounds were confirmed by spectral (UV-Vis, FT-IR, MS, 1H- and 13C-NMR) data and elemental analysis results, and their purity was determined by RP-HPLC. The new compounds were assessed for their antimicrobial activity and toxicity to aquatic crustacean Daphnia magna. Also, in silico studies regarding their potential mechanism of action and toxicity were performed. The antimicrobial evaluation revealed that the 2-{4-[(4-chlorophenyl)sulfonyl]benzamido}-3-methylbutanoic acid and the corresponding 1,3-oxazol-5(4H)-one exhibited antimicrobial activity against Gram-positive bacterial strains and the new 1,3-oxazole containing a phenyl group at 5-position against the C. albicans strain.


Assuntos
Anti-Infecciosos/síntese química , Anti-Infecciosos/toxicidade , Ácido Benzoico/síntese química , Ácido Benzoico/toxicidade , Simulação por Computador , Animais , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Ácido Benzoico/química , Ácido Benzoico/farmacologia , Biofilmes/efeitos dos fármacos , Daphnia/efeitos dos fármacos , Avaliação Pré-Clínica de Medicamentos , Testes de Sensibilidade Microbiana , Espectroscopia de Prótons por Ressonância Magnética , Testes de Toxicidade
7.
Molecules ; 26(13)2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34279443

RESUMO

Diterpenoid alkaloids are natural compounds having complex structural features with many stereo-centres originating from the amination of natural tetracyclic diterpenes and produced primarily from plants in the Aconitum, Delphinium, Consolida genera. Corals, Xenia, Okinawan/Clavularia, Alcyonacea (soft corals) and marine sponges are rich sources of diterpenoids, despite the difficulty to access them and the lack of availability. Researchers have long been concerned with the potential beneficial or harmful effects of diterpenoid alkaloids due to their structural complexity, which accounts for their use as pharmaceuticals as well as their lousy reputation as toxic substances. Compounds belonging to this unique and fascinating family of natural products exhibit a broad spectrum of biological activities. Some of these compounds are on the list of clinical drugs, while others act as incredibly potent neurotoxins. Despite numerous attempts to prepare synthetic products, this review only introduces the natural diterpenoid alkaloids, describing 'compounds' structures and classifications and their toxicity and bioactivity. The purpose of the review is to highlight some existing relationships between the presence of substituents in the structure of such molecules and their recognised bioactivity.


Assuntos
Alcaloides/farmacologia , Produtos Biológicos/farmacologia , Diterpenos/farmacologia , Animais , Anti-Infecciosos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Humanos , Testes de Toxicidade
8.
Molecules ; 26(14)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34299388

RESUMO

In a project designed to investigate the specific and infraspecific taxa of Matthiola endemic to Sicily (Italy) as new potential sources of bioactive compounds in this work, the infraspecific taxa of Matthiola fruticulosa were studied, namely, subsp. fruticulosa and subsp. coronopifolia. HPLC-PDA/ESI-MS and SPME-GC/MS analyses of hydroalcoholic extracts obtained from the aerial parts of the two subspecies led to the detection of 51 phenolics and 61 volatile components, highlighting a quite different qualitative-quantitative profile. The antioxidant properties of the extracts were explored through in vitro methods: 1,1-diphenyl-2-picrylhydrazyl (DPPH), reducing power and Fe2+ chelating activity assays. The results of the antioxidant tests showed that the extracts possess a different antioxidant ability: particularly, the extract of M. fruticulosa subsp. fruticulosa exhibited higher radical scavenging activity than that of subsp. coronopifolia (IC50 = 1.25 ± 0.02 mg/mL and 2.86 ± 0.05 mg/mL), which in turn displayed better chelating properties (IC50 = 1.49 ± 0.01 mg/mL and 0.63 ± 0.01 mg/mL). Lastly, Artemia salina lethality bioassay was performed for toxicity assessment. The results of the bioassay showed lack of toxicity against brine shrimp larvae for both extracts. The data presented indicate the infraspecific taxa of M. fruticulosa as new and safe sources of antioxidant compounds.


Assuntos
Antioxidantes/toxicidade , Brassicaceae/química , Larva/crescimento & desenvolvimento , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/toxicidade , Extratos Vegetais/toxicidade , Animais , Artemia , Larva/efeitos dos fármacos , Sicília , Testes de Toxicidade
9.
Toxicol Lett ; 350: 152-161, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34311048

RESUMO

As nephrogenic systemic fibrosis (NSF) and increased signal intensities in deep cerebellar nuclei (DCN) were successively discovered in renal insufficiency patients and healthy persons after gadolinium-based contrast agents (GBCAs) exposure, an awareness of potential toxicity with GBCAs exposure has been heightening. Herein, we performed a multi-organ/tissue toxicity assessment after different GBCAs administration with a large number of samples, and long-term, time-course schedule investigation. ICR mice were randomized to five exposure groups (n = 42/group) and received intravenous injection of GBCAs (2.5 mmol Gd/kg) or saline four time a week for 5 consecutive weeks. Gadolinium concentration detection, sensory tests, histological and hematological analyses were performed at corresponding timepoints (4th or 6th or 10th week). Our results showed that (i) gadodiamide could cause reversible vacuolar changes in the renal tubular epithelial cells, which appeared at 6th week and recovered at 10th week, and severe skin lesion in mice tail with consecutive injection for 10 weeks, that (ii) linear GBCAs (gadodiamide and gadopentetate dimeglumine) markedly elevated heat hyperalgesia and white blood cells of mice at 6th week and most of these changes could recovery at 10th week, and that (iii) linear GBCAs exhibited more gadolinium retention in multi-organ/tissue versus macrocyclic GBCAs and in most case, linear GBCAs showed faster accumulation and regression speed in examined tissues than macrocyclic GBCAs excepting gadodiamide in skin which showed slowest regression speed. Collectively, macrocyclic GBCAs presents more stable, lower propensity to release Gd and safer profiles versus linear GBCAs.


Assuntos
Estruturas Animais/citologia , Estruturas Animais/efeitos dos fármacos , Meios de Contraste/toxicidade , Gadolínio/toxicidade , Compostos Macrocíclicos/toxicidade , Estrutura Molecular , Animais , Feminino , Camundongos , Camundongos Endogâmicos ICR , Modelos Animais , Testes de Toxicidade
10.
Bull Environ Contam Toxicol ; 107(3): 494-499, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34269820

RESUMO

Soil toxicity tests are commonly applied using Enchytraeus crypticus to analyze reproductive outputs. However, the traditional method for counting potworms takes a long time due to the significant number of offspring. This paper compares the conventional total counting of E. crypticus juveniles (M1) and an alternative methodology (M2). The proposed methodology (M2) uses a simple random counting method (1/4) for the partial counting of juveniles and total estimation. Chronic bioassays (21 days of exposure) were performed in tropical artificial soil (TAS) using sugarcane vinasse as a hazardous substance. Comparing the final density of juveniles recorded in M1 and M2, no statistical differences were pointed out in either one. Applying analyses based on effective concentration (EC10 and EC50), no statistical differences were identified there either. The t-test showed that there was no statistical difference between the counting methods (M1 and M2) in each treatment (control and dilutions). Moreover, we ran the Tukey test for M1 and M2 methods separately and observed that 100 % of the vinasse showed a statistical difference compared to the control treatment in both (p ≤ 0.05), affirming that independent of the counting method, the ecotoxicological outputs were similar. Therefore, the proposed alternative is a suitable method for bioassay using. E. crypticus in tropical artificial soil, decreasing to 1/4 the total time required for counting.


Assuntos
Oligoquetos , Poluentes do Solo , Animais , Ecotoxicologia , Reprodução , Solo , Poluentes do Solo/análise , Poluentes do Solo/toxicidade , Testes de Toxicidade
11.
Toxicology ; 458: 152846, 2021 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-34216698

RESUMO

The 3Rs concept, calling for replacement, reduction and refinement of animal experimentation, is receiving increasing attention around the world, and has found its way to legislation, in particular in the European Union. This is aligned by continuing high-level efforts of the European Commission to support development and implementation of 3Rs methods. In this respect, the European project called "ONTOX: ontology-driven and artificial intelligence-based repeated dose toxicity testing of chemicals for next generation risk assessment" was recently initiated with the goal to provide a functional and sustainable solution for advancing human risk assessment of chemicals without the use of animals in line with the principles of 21st century toxicity testing and next generation risk assessment. ONTOX will deliver a generic strategy to create new approach methodologies (NAMs) in order to predict systemic repeated dose toxicity effects that, upon combination with tailored exposure assessment, will enable human risk assessment. For proof-of-concept purposes, focus is put on NAMs addressing adversities in the liver, kidneys and developing brain induced by a variety of chemicals. The NAMs each consist of a computational system based on artificial intelligence and are fed by biological, toxicological, chemical and kinetic data. Data are consecutively integrated in physiological maps, quantitative adverse outcome pathway networks and ontology frameworks. Supported by artificial intelligence, data gaps are identified and are filled by targeted in vitro and in silico testing. ONTOX is anticipated to have a deep and long-lasting impact at many levels, in particular by consolidating Europe's world-leading position regarding the development, exploitation, regulation and application of animal-free methods for human risk assessment of chemicals.


Assuntos
Inteligência Artificial , Ontologia Genética , Testes de Toxicidade , Alternativas aos Testes com Animais , Animais , Simulação por Computador , União Europeia , Humanos , Técnicas In Vitro , Medição de Risco
12.
Int J Mol Sci ; 22(12)2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34198694

RESUMO

Plasmonic nanoparticles are increasingly employed in several fields, thanks to their unique, promising properties. In particular, these particles exhibit a surface plasmon resonance combined with outstanding absorption and scattering properties. They are also easy to synthesize and functionalize, making them ideal for nanotechnology applications. However, the physicochemical properties of these nanoparticles can make them potentially toxic, even if their bulk metallic forms are almost inert. In this review, we aim to provide a more comprehensive understanding of the potential adverse effects of plasmonic nanoparticles in zebrafish (Danio rerio) during both development and adulthood, focusing our attention on the most common materials used, i.e., gold and silver.


Assuntos
Modelos Animais , Nanopartículas/toxicidade , Testes de Toxicidade , Animais , Tamanho da Partícula , Peixe-Zebra
13.
Int J Mol Sci ; 22(13)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209790

RESUMO

We developed a multi-channel cell chip containing a three-dimensional (3D) scaffold for horizontal co-culture and drug toxicity screening in multi-organ culture (human glioblastoma, cervical cancer, normal liver cells, and normal lung cells). The polydimethylsiloxane (PDMS) multi-channel cell chip (PMCCC) was based on fused deposition modeling (FDM) technology. The architecture of the PMCCC was an open-type cell chip and did not require a pump or syringe. We investigated cell proliferation and cytotoxicity by conducting 3-(4,5-dimethylthiazol-2-yl)-2,5-dphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays and analysis of oleanolic acid (OA)-treated multi-channel cell chips. The results of the MTT and LDH assays showed that OA treatment in the multi-channel cell chip of four cell lines enhanced chemoresistance of cells compared with that in the 2D culture. Furthermore, we demonstrated the feasibility of the application of our multi-channel cell chip in various analysis methods through Annexin V-fluorescein isothiocyanate/propidium iodide staining, which is not used for conventional cell chips. Taken together, the results demonstrated that the PMCCC may be used as a new 3D platform because it enables simultaneous drug screening in multiple cells by single point injection and allows analysis of various biological processes.


Assuntos
Técnicas de Cultura de Células , Avaliação Pré-Clínica de Medicamentos , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Linhagem Celular Tumoral , Proliferação de Células , Tamanho Celular , Técnicas de Cocultura/instrumentação , Técnicas de Cocultura/métodos , Avaliação Pré-Clínica de Medicamentos/instrumentação , Avaliação Pré-Clínica de Medicamentos/métodos , Células HeLa , Humanos , Dispositivos Lab-On-A-Chip , Teste de Materiais , Tecidos Suporte/química , Testes de Toxicidade/instrumentação , Testes de Toxicidade/métodos
14.
Crit Rev Toxicol ; 51(4): 328-358, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-34074207

RESUMO

The current understanding of thyroid-related adverse outcome pathways (AOPs) with adverse neurodevelopmental outcomes in mammals has been reviewed. This served to establish if standard rodent toxicity test methods and in vitro assays allow identifying thyroid-related modes-of-action potentially leading to adverse neurodevelopmental outcomes, and the human relevance of effects - in line with the European Commission's Endocrine Disruptor Criteria. The underlying hypothesis is that an understanding of the key events of relevant AOPs provides insight into differences in incidence, magnitude, or species sensitivity of adverse outcomes. The rodent studies include measurements of serum thyroid hormones, thyroid gland pathology and neurodevelopmental assessments, but do not directly inform on specific modes-of-action. Opportunities to address additional non-routine parameters reflecting critical events of AOPs in toxicological assessments are presented. These parameters appear relevant to support the identification of specific thyroid-related modes-of-action, provided that prevailing technical limitations are overcome. Current understanding of quantitative key event relationships is often weak, but would be needed to determine if the triggering of a molecular initiating event will ultimately result in an adverse outcome. Also, significant species differences in all processes related to thyroid hormone signalling are evident, but the biological implications thereof (including human relevance) are often unknown. In conclusion, careful consideration of the measurement (e.g. timing, method) and interpretation of additional non-routine parameters is warranted. These findings will be used in a subsequent paper to propose a testing strategy to identify if a substance may elicit maternal thyroid hormone imbalance and potentially also neurodevelopmental effects in the progeny.


Assuntos
Testes de Toxicidade/métodos , Rotas de Resultados Adversos , Animais , Disruptores Endócrinos , Humanos , Sistema Nervoso/efeitos dos fármacos , Sistema Nervoso/crescimento & desenvolvimento , Síndromes Neurotóxicas , Medição de Risco , Glândula Tireoide , Hormônios Tireóideos
15.
Sci Total Environ ; 790: 148223, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34111781

RESUMO

A comprehensive study of the toxicity of lanthanides (LN) in relation to the media composition will enhance the prediction of their potential adverse effects for living organisms. Here we examined the effect of different media on the V. faba root elongation and on the cytotoxic (mitotic index) and the genotoxic (micronucleated cell number) effects from toxicity tests with Ce, Gd and Lu (100, 800 and 6400 µg L-1). Three different exposure media were selected: the standard Hoagland media (SH); an alternative SH, without phosphates (SH-P); and distilled water (DW). In the SH no cyto-genotoxic effects were observed and even, for low LN content, potential root elongation stimulation was reported. The absence of toxic effects was explained by a drastic decrease of the total dissolved LN concentration due to the presence of phosphates causing LN precipitation. In SH-P, LN remained largely soluble and inhibition of root elongation was observed mainly for the highest treatments. While in the tests done in DW, toxic effects were obtained for all treatments. Our results showed that in absence of phosphorous, LN appear mainly as free form and complexed in carbonates and sulphates, and can cause toxic effects, whereas toxicity is not expected when phosphorous is available in aquatic media. The highest LN root contents were observed for the tests using distilled water, possibly due to the absence of competition by Ca2+ for uptake. The present work demonstrated that media composition has a great impact in assessing the ecotoxicology of lanthanides.


Assuntos
Elementos da Série dos Lantanídeos , Vicia faba , Dano ao DNA , Ecotoxicologia , Raízes de Plantas , Testes de Toxicidade
16.
J Toxicol Environ Health A ; 84(17): 710-728, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34102960

RESUMO

In vivo animal bioassays are increasingly being supplemented with in vitro assays to serve as the new standard for chemical toxicity tests. Despite this shift, investigators face challenges related to increased reliance on in vitro data. The aim of this study was to deploy a streamlined method to assess the ability of in vitro data to predict similar results as in vivo data by correlating chemical toxicity rankings obtained using Benchmark Doses and Benchmark Dose Lower Limits (BMD(L)s) derived from in vivo and in vitro assays. In vitro and in vivo assay characteristics were assessed for their impact on the predictive ability of in vitro data. Minimum best-fit BMD(L)s were calculated for chemicals using Environmental Protection Agency's (EPA's) Benchmark Dose Software (BMDS). Forty-one chemicals met the inclusion criteria of this study. Relative chemical toxicity rankings were assessed through Kappa statistics, Pearson correlations, and/or Ordinary Least Squares (OLS) regressions. Results illustrated likely ability of in vitro data to predict similar results as short-term in vivo data. Further, rankings derived from in vitro cytotoxicity assays, unlike stress response assays, significantly correlated with rankings derived from short-term in vivo assays. These results support the use of in vitro data as a prioritization tool within toxicity testing.


Assuntos
Ecotoxicologia/métodos , Técnicas In Vitro/estatística & dados numéricos , Testes de Toxicidade/métodos , Benchmarking/métodos , Ecotoxicologia/instrumentação , Testes de Toxicidade/instrumentação
17.
Molecules ; 26(9)2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34062815

RESUMO

Aza-porphyrinoids exhibit distinct spectral properties in UV-Vis, and they are studied in applications such as photosensitizers in medicine and catalysts in technology. The use of appropriate peripheral substituents allows the modulation of their physicochemical properties. Phthalocyanine and sulfanyl porphyrazine octa-substituted with 4-(butoxycarbonyl)phenyloxy moieties were synthesized and characterized using UV-Vis and NMR spectroscopy, as well as mass spectrometry. A comparison of porphyrazine with phthalocyanine aza-porphyrinoids revealed that phthalocyanine macrocycle exhibits higher singlet oxygen generation quantum yields, reaching the value of 0.29 in DMF. After both macrocycles had been deposited on titanium dioxide nanoparticles P25, the cytotoxicities and photocytotoxicities of the prepared materials were studied using a Microtox® acute toxicity test. The highest cytotoxicity occurred after irradiation with a red light for the material composed of phthalocyanine deposited on titania nanoparticles.


Assuntos
Indóis/química , Nanopartículas Metálicas/química , Parabenos/química , Porfirinas/química , Titânio/química , Anti-Infecciosos/administração & dosagem , Antineoplásicos/administração & dosagem , Sobrevivência Celular , Desenho de Fármacos , Espectroscopia de Ressonância Magnética , Nanomedicina/métodos , Nanopartículas/química , Neoplasias/tratamento farmacológico , Tamanho da Partícula , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/química , Solventes , Testes de Toxicidade , Raios Ultravioleta
18.
Methods Mol Biol ; 2326: 19-32, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097258

RESUMO

The contamination of heavy metals, a class of naturally occurring and persistent toxicants, has become a major public health concern due to increasing industrial and anthropogenic activities. The use of COPAS Biosort, a flow cytometer capable of measuring thousands of nematodes in minutes via high-throughput assays, has been widely applied in C. elegans studies for assessing toxicity of individual metals; however, such application yet to be seen for metals or other chemical mixtures. In the present protocol, we investigated toxic effects of individual metals, Cd, Pb, and Mn, as well as their binary and ternary mixtures, using nematode C. elegans. The toxic outcomes, including effects on growth, reproduction, and feeding behavior, were measured using high-throughput platform analysis (COAPS Biosort).


Assuntos
Cádmio/toxicidade , Caenorhabditis elegans/efeitos dos fármacos , Chumbo/toxicidade , Manganês/toxicidade , Animais , Caenorhabditis elegans/crescimento & desenvolvimento , Caenorhabditis elegans/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Ensaios de Triagem em Larga Escala/métodos , Reprodução/efeitos dos fármacos , Testes de Toxicidade/métodos
19.
Methods Mol Biol ; 2326: 33-46, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097259

RESUMO

Environmental pollutants inevitably exert adverse effects on humans and other species. Quick identification and in-depth characterization of the pollutants are requisite objectives for clinicians and environmental health scientists. The nematode Caenorhabditis elegans has been utilized as a model organism for toxicity evaluation of environmental pollutants, due to its transparency, short lifespan, entire genome sequencing, and economical characteristics. However, few researchers have systematically addressed mitochondrial toxicity in response to toxicants, despite the critical role mitochondria play in energy production and respiration, as well as the generation of reactive oxygen species. Mitochondria are vulnerable to environmental pollutants, and their dysfunction contributes to cellular damage and toxicity in plethora of diseases. Here, we describe methods in step-by-step for mitochondrial toxicity evaluation in response to pollutants, including exposure of C. elegans to toxicants, mitochondrial ROS detection, mitochondrial morphology analysis, mitochondrial function analysis, such as ATP production and oxygen consumption, and gene expression studies, with the application of corresponding genetically modified strains.


Assuntos
Caenorhabditis elegans/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Mitocôndrias/efeitos dos fármacos , Trifosfato de Adenosina/metabolismo , Animais , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Expressão Gênica/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Mitocôndrias/ultraestrutura , Consumo de Oxigênio/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade/métodos
20.
Methods Mol Biol ; 2326: 47-54, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097260

RESUMO

Drosophila melanogaster, the fruit fly, has been widely used in biological investigation as an invertebrate alternative to mammals for its various advantages compared to other model organisms, which include short life cycle, easy handling, high prolificacy, and great availability of substantial genetic information. The behavior of Drosophila melanogaster is closely related to its growth, which can reflect the physiological conditions of Drosophila. We have optimized simple and robust behavioral assays for determining the larvae survival, adult climbing ability (mobility assay), reproductive behavior, and lifespan of Drosophila. In this chapter, we present the step-by-step detailed method for studying Drosophila behavior.


Assuntos
Drosophila melanogaster/fisiologia , Animais , Bioensaio/métodos , Drosophila melanogaster/efeitos dos fármacos , Drosophila melanogaster/crescimento & desenvolvimento , Feminino , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Larva/fisiologia , Locomoção/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Masculino , Reprodução/efeitos dos fármacos , Testes de Toxicidade/métodos
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