Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 292
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
4.
Biotechnol J ; 14(8): e1800724, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31106963

RESUMO

Oxygenase-containing cyanobacteria constitute promising whole-cell biocatalysts for oxyfunctionalization reactions. Photosynthetic water oxidation thereby delivers the required cosubstrates, that is activated reduction equivalents and O2 , sustainably. A recombinant Synechocystis sp. PCC 6803 strain showing unprecedentedly high photosynthesis-driven oxyfunctionalization activities is developed, and its technical applicability is evaluated. The cells functionally synthesize a heterologous cytochrome P450 monooxygenase enabling cyclohexane hydroxylation. The biocatalyst-specific reaction rate is found to be light-dependent, reaching 26.3 ± 0.6 U gCDW -1 (U = µmol min-1 and cell dry weight [CDW]) at a light intensity of 150 µmolphotons m-2 s-1 . In situ substrate supply via a two-liquid phase system increases the initial specific activity to 39.2 ± 0.7 U gCDW -1 and stabilizes the biotransformation by preventing cell toxification. This results in a tenfold increased specific product yield of 4.5 gcyclohexanol gCDW -1 as compared to the single aqueous phase system. Subsequently, the biotransformation is scaled from a shake flask to a 3 L stirred-tank photobioreactor setup. In situ O2 generation via photosynthetic water oxidation allows a nonaerated process operation, thus circumventing substrate evaporation as the most critical factor limiting the process performance and stability. This study for the first time exemplifies the technical applicability of cyanobacteria for aeration-independent light-driven oxyfunctionalization reactions involving highly toxic and volatile substrates.


Assuntos
Cicloexanos/metabolismo , Cicloexanóis/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Synechocystis/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biocatálise , Biotecnologia/instrumentação , Biotecnologia/métodos , Biotransformação , Meios de Cultura/química , Cicloexanos/toxicidade , Hidroxilação , Luz , Microrganismos Geneticamente Modificados , Oxigenases de Função Mista/metabolismo , Oxigênio/metabolismo , Fotobiorreatores , Synechocystis/efeitos dos fármacos , Synechocystis/genética
5.
Chemosphere ; 231: 301-307, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31129411

RESUMO

Brominated flame-retardants are environmentally pervasive and persistent synthetic chemicals, some of which have been demonstrated to disrupt neuroendocrine signaling and electrical activity of neurons. 1,2-dibromo-4-(1,2-dibromoethyl)-cyclohexane (TBECH) lacks the toxicity of other classes of BFRs, however its safety is still questioned, as little is known of its neurological effects. Therefore, we sought to determine if TBECH could acutely alter the electrical activity of Purkinje neurons maintained in vitro. Briefly, cerebella from gestational day 20 rats were dissociated and maintained for up to three weeks in culture. Action potentials of Purkinje neurons were detected by cell-attached patch clamp before, during, and after application of ß-TBECH. ß-TBECH decreased action potential activity in a dose-dependent manner with an apparent EC50 of 396 nM. ß-TBECH did not significantly alter the coefficient of variation, a measure of the regularity of firing, suggesting that the mechanism of ß-TBECH's effects on firing frequency may be independent of Purkinje neuron intracellular calcium handling. Because levels of ß-TBECH in exposed individuals may not approach the EC50, these data suggest that any abnormal neurodevelopment or behavior linked with ß-TBECH exposure may result from endocrinological effects as opposed to direct disruption of electrical activity.


Assuntos
Cicloexanos/toxicidade , Retardadores de Chama/toxicidade , Testes de Toxicidade Aguda , Animais , Halogenação , Masculino , Células de Purkinje , Ratos
8.
Ecotoxicol Environ Saf ; 169: 770-777, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30597775

RESUMO

The current-use brominated flame retardant, 1,2-dibromo-4-(1,2-dibromoethyl)cyclohexane (DBE-DBCH), is capable of perturbing sex steroid and thyroid hormone pathways in vitro and in vivo. Chemicals with this capability may also disrupt metabolic processes and are candidate obesogens, but this potential has not yet been determined for DBE-DBCH. Our objective was to examine gross biomarkers of metabolic disruption in captive American kestrels. Birds were exposed by diet to the ß isomer at the environmentally relevant dose of 0.239 ng ß-DBE-DBCH/g kestrel/day, from 30 days (d) prior to pairing through until chicks hatched (82 d) (n = 30 breeding pairs) or for 28 d (n = 16 pre-breeding pairs), and were compared with vehicle-only exposed controls. Body mass was assessed throughout the breeding season at biologically relevant time points, flight and feeding behavior was measured in 5-min samples daily, and plasma triglycerides and cholesterol were assessed at d10 of brood rearing. Treated males were heavier than controls at pairing (p = 0.051), the final week of courtship (p = 0.061), and at d10 (p = 0.012) and d20 of brood rearing (p = 0.051); ß-DBE-DBCH-exposed breeding females were similar in weight to control females. Treated birds tended to have higher plasma triglycerides (p = 0.078), which for females, was positively associated with body mass (p = 0.019). Heavier breeding males had higher plasma concentrations of testosterone and total thyroxine (p ≤ 0.046). Overall, both sexes exposed to ß-DBE-DBCH demonstrated reduced flight behavior and increased feeding behavior during courtship. In the pre-breeding pairs, treated male and female kestrels had a higher percentage of body fat than respective controls (p = 0.045). These results demonstrate that ß-DBE-DBCH elicited inappropriate fat and weight gain in adult American kestrels, consistent with their increased feeding, reduced flight activity and endocrine changes, and suggests that DBE-DBCH may be an obesogen warranting further research to test this hypothesis.


Assuntos
Cicloexanos/toxicidade , Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Falconiformes/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Retardadores de Chama/toxicidade , Voo Animal/efeitos dos fármacos , Animais , Distribuição da Gordura Corporal , Disruptores Endócrinos/metabolismo , Poluentes Ambientais/metabolismo , Falconiformes/crescimento & desenvolvimento , Falconiformes/metabolismo , Feminino , Retardadores de Chama/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Masculino , Testosterona/sangue , Tiroxina/sangue , Testes de Toxicidade
9.
Artigo em Inglês | MEDLINE | ID: mdl-30528700

RESUMO

Tetrabromoethylcyclohexane (TBECH), as one emerging brominated flame retardants, is ubiquitous in the environment, including water and aquatic organisms. TBECH was found to exhibit endocrine-disrupting effects in different models, whereas a survey of comprehensive toxic effects of TBECH on zebrafish is limited. In the present study, zebrafish (Danio rerio) were waterborne exposed continuously to TBECH from embryonic stage (3 h post-fertilization (hpf)) to the time when the respective parameters were evaluated. Exposure to TBECH reduced hatchability of zebrafish embryos at 72 and 96 hpf, diminished heart rate of zebrafish larvae at 48 hpf, and increased malformation in zebrafish larvae at 96 hpf. In addition, exposure to TBECH diminished free swimming distance both in the light and under a photoperiod of 10 min light/10 min dark cycles in zebrafish larvae at 6 days post-fertilization (dpf). Moreover, exposure to TBECH elevated activities of superoxide dismutase (SOD) and catalase (CAT), malondialdehyde (MDA) content, whereas it reduced glutathione (GSH) content, in zebrafish larvae at 6 dpf. Accordingly, RT-qPCR analysis demonstrated that TBECH exposure increased the mRNA levels of sod1, sod2, cat, and gpx1 in zebrafish larvae at 6 dpf. With respect to the immune aspect, the mRNA levels of pro-inflammatory genes, including il-1b, il-6, il-8, and tnfa, in larval zebrafish at 6 dpf were increased by exposure to TBECH, while pretreatment with TBECH inhibited 24 h of exposure to LPS-stimulated elevation in the mRNA levels of the abovementioned four pro-inflammatory genes in zebrafish larvae at 6 dpf. Furthermore, TBECH treatment increased caspase-3 enzyme activities and regulated apoptosis-related genes in larval zebrafish at 6 dpf. Taken together, the data obtained in this study demonstrated that TBECH caused developmental and locomotor behavioral toxicity, immunotoxicity, oxidative stress and proapoptotic effects in early life zebrafish. The present study will help to understand the comprehensive toxicity of TBECH in zebrafish.


Assuntos
Cicloexanos/toxicidade , Embrião não Mamífero/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Animais , Caspase 3 , Catalase , Cicloexanos/administração & dosagem , Retardadores de Chama/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Glutationa , Larva/efeitos dos fármacos , Malondialdeído , Superóxido Dismutase , Poluentes Químicos da Água/administração & dosagem , Peixe-Zebra/embriologia
10.
Nat Commun ; 9(1): 4815, 2018 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-30446643

RESUMO

Common disorders, including diabetes and Parkinson's disease, are caused by a combination of environmental factors and genetic susceptibility. However, defining the mechanisms underlying gene-environment interactions has been challenging due to the lack of a suitable experimental platform. Using pancreatic ß-like cells derived from human pluripotent stem cells (hPSCs), we discovered that a commonly used pesticide, propargite, induces pancreatic ß-cell death, a pathological hallmark of diabetes. Screening a panel of diverse hPSC-derived cell types we extended this observation to a similar susceptibility in midbrain dopamine neurons, a cell type affected in Parkinson's disease. We assessed gene-environment interactions using isogenic hPSC lines for genetic variants associated with diabetes and Parkinson's disease. We found GSTT1-/- pancreatic ß-like cells and dopamine neurons were both hypersensitive to propargite-induced cell death. Our study identifies an environmental chemical that contributes to human ß-cell and dopamine neuron loss and validates a novel hPSC-based platform for determining gene-environment interactions.


Assuntos
Cicloexanos/toxicidade , Diabetes Mellitus/induzido quimicamente , Neurônios Dopaminérgicos/efeitos dos fármacos , Interação Gene-Ambiente , Células Secretoras de Insulina/efeitos dos fármacos , Praguicidas/toxicidade , Animais , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Diferenciação Celular , Diabetes Mellitus/genética , Diabetes Mellitus/patologia , Neurônios Dopaminérgicos/citologia , Neurônios Dopaminérgicos/enzimologia , Glutationa Transferase/deficiência , Glutationa Transferase/genética , Humanos , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/enzimologia , Mesencéfalo/citologia , Mesencéfalo/efeitos dos fármacos , Mesencéfalo/enzimologia , Camundongos , Modelos Biológicos , Doença de Parkinson/etiologia , Doença de Parkinson/genética , Doença de Parkinson/patologia , Células-Tronco Pluripotentes/citologia , Células-Tronco Pluripotentes/enzimologia
12.
Artigo em Inglês | MEDLINE | ID: mdl-30597898

RESUMO

The present study aims to evaluate the potential for the pollution of the environment by two herbicides (quizalofop-p-ethyl and cycloxydim), using the Allium test. The species in question is Allium cepa (onion, 2n = 16), one of the most common plant indicators of environmental pollution. The working method consisted of obtaining the meristematic roots of Allium cepa and their treatment with herbicides at three different concentrations (0.5%, 1%, and 1.5%) for each herbicide for 24 h, for comparison with an untreated control. The results obtained from the cytological study indicated a strong cytotoxic and genotoxic effect for both herbicides, but especially for quizalofop-p-ethyl, where the mitotic index decreased from 30.2% (control) to 9.6% for the variant treated with 1.5% herbicide. In this case, a strong mitodepressive effect was shown by a highly significant percentage (35.4%) of chromosomal aberrations and nuclear alterations: stickiness, fragments, C-mitosis, lobulated nucleus, micronuclei, and nuclear erosion. The mitodepressive effect as well as the percentage of chromosomal aberrations increased with a higher herbicide concentration. The obtained results suggest the strong potential for pollution of the two herbicides, particularly at concentrations higher than 0.5%; therefore, we recommend caution in their use to avoid undesirable effects on the environment.


Assuntos
Poluentes Ambientais/toxicidade , Herbicidas/toxicidade , Cebolas/efeitos dos fármacos , Cicloexanos/toxicidade , Dano ao DNA/efeitos dos fármacos , Mitose/efeitos dos fármacos , Cebolas/citologia , Cebolas/genética , Raízes de Plantas/citologia , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/genética , Propionatos/toxicidade , Piranos/toxicidade , Quinoxalinas/toxicidade
15.
Chemosphere ; 188: 599-607, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28917212

RESUMO

On January 9, 2014, a chemical mixture containing crude methylcyclohexanemethanol (MCHM) contaminated the water supply of Charleston, West Virginia. Although the mixture was later identified as a mix of crude MCHM and stripped propylene glycol phenyl ethers, initial risk assessment focused on 4-MCHM, the predominant component of crude MCHM. The mixture's exact composition and the toxicity differences between 4-MCHM, crude MCHM, and the tank mixture were unknown. We analyzed the chemical composition of crude MCHM and the tank mixture via GC/MS and, based on identified spectra, found that crude MCHM and the tank mixture differed in chemical composition. To evaluate acute developmental toxicity, zebrafish embryos were exposed to 0, 1, 6.25, 12.5, 25, 50, or 100 parts per million (ppm; mg/L) of 4-MCHM, crude MCHM, or the tank mixture. The percent mortality and percent hatch, larval morphology alterations, and larval visual motor response test were used to establish toxicity profiles for each of the chemicals or mixtures. The acute toxicity differed between 4-MCHM, crude MCHM and the tank mixture with significant differences in survival, hatching, morphology, and locomotion at levels as low as the short-term screening level of 1 ppm, suggesting a need for further research into human health risks. This study is the first to evaluate the developmental toxicity of the tank mixture and highlights that studies evaluating risk should not assume the effects of 4-MCHM or crude MCHM are representative of the Tank 396 mixture.


Assuntos
Vazamento de Resíduos Químicos , Cicloexanos/toxicidade , Rios/química , Poluentes Químicos da Água/análise , Animais , Cicloexanos/análise , Exposição Ambiental , Cromatografia Gasosa-Espectrometria de Massas , Éteres Fenílicos , Abastecimento de Água/normas , West Virginia , Peixe-Zebra/embriologia
16.
Aquat Toxicol ; 192: 40-47, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28917944

RESUMO

Tetrabromoethylcyclohexane (TBECH), an additive brominated flame retardant, has been shown to have an androgenic activity in vitro. In the present study, we aimed to investigate the effects of TBECH on gonadal differentiation and development in the frog Pelophylax nigromaculatus, an amphibian species sensitive to androgenic chemicals, and to assess the androgenic activity of TBECH in vivo. P. nigromaculatus tadpoles were exposed to TBECH (1, 10, 100nM) from Gosner stage 24 to complete metamorphosis, and to 5α-dihydrotestosterone (DHT) as a positive control. We found that 1nM DHT resulted in 100% males, while the sex ratio in the solvent control group was close to 1:1. In all the TBECH treatment groups, sexually ambiguous gonads based on gross morphology and intersexualities with testicular and ovarian histological structures were found, but no abnormality occurred in the solvent control. In the 1, 10, 100nM TBECH treatment groups, the female percentages were 52%, 31%, 17%, with 36%, 56%, 66% for males and 12%, 13%, 17% for abnormal sexes, respectively. X2-test revealed significant differences in sex ratios between the three TBECH groups and the solvent control group, and the sex ratios in the two higher concentration groups were male-biased. These observations show that TBECH has a masculinizing effect on gonadal differentiation and development in P. nigromaculatus, suggesting an androgenic activity of TBECH in vivo. To our knowledge, this is the first study demonstrating that TBECH could induce gonadal masculinization in an animal, which raises new concerns for reproductive risk of TBECH exposure.


Assuntos
Cicloexanos/toxicidade , Retardadores de Chama/toxicidade , Ranidae , Poluentes Químicos da Água/toxicidade , Animais , Transtornos do Desenvolvimento Sexual/induzido quimicamente , Feminino , Larva/efeitos dos fármacos , Larva/crescimento & desenvolvimento , Masculino , Metamorfose Biológica/efeitos dos fármacos , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Ranidae/crescimento & desenvolvimento , Razão de Masculinidade , Testículo/efeitos dos fármacos , Testículo/crescimento & desenvolvimento
17.
Reprod Toxicol ; 70: 82-96, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28527947

RESUMO

Embryonic vascular disruption is an important adverse outcome pathway (AOP) as chemical disruption of cardiovascular development induces broad prenatal defects. High throughput screening (HTS) assays aid AOP development although linking in vitro data to in vivo apical endpoints remains challenging. This study evaluated two anti-angiogenic agents, 5HPP-33 and TNP-470, across the ToxCastDB HTS assay platform and anchored the results to complex in vitro functional assays: the rat aortic explant assay (AEA), rat whole embryo culture (WEC), and the zebrafish embryotoxicity (ZET) assay. Both were identified as putative vascular disruptive compounds (pVDCs) in ToxCastDB and disrupted angiogenesis and embryogenesis in the functional assays. Differences were observed in potency and adverse effects: 5HPP-33 was embryolethal (WEC and ZET); TNP-470 produced caudal defects at lower concentrations. This study demonstrates how a tiered approach using HTS signatures and complex functional in vitro assays might be used to prioritize further in vivo developmental toxicity testing.


Assuntos
Inibidores da Angiogênese/toxicidade , Sistema Cardiovascular/efeitos dos fármacos , Cicloexanos/toxicidade , Ensaios de Triagem em Larga Escala , Isoindóis/toxicidade , Neovascularização Fisiológica/efeitos dos fármacos , Sesquiterpenos/toxicidade , Teratogênios/toxicidade , Animais , Aorta Torácica/efeitos dos fármacos , Aorta Torácica/fisiologia , Sistema Cardiovascular/embriologia , Desenvolvimento Embrionário/efeitos dos fármacos , O-(Cloroacetilcarbamoil)fumagilol , Organogênese/efeitos dos fármacos , Coelhos , Ratos
18.
Cutan Ocul Toxicol ; 36(4): 351-355, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28277879

RESUMO

Crude 4-methylcyclohexanemethanol (MCHM) is an industrial chemical used to wash and clean coal. On January 9th, 2014 approximately 10,000 gallons of a mixture containing crude MCHM were released into the Elk River near Charleston, West Virginia, contaminating the local water supply. Following the spill, residents reported numerous health complaints, and sought medical attention for ailments including rashes and itching. The relationship between the complaints and the spill were unknown, as such symptoms are reported frequently in the background. In this study, the primary irritation potential of crude MCHM was evaluated in 206 individuals who underwent 48 hour semi-occluded patch testing. MCHM concentrations assessed in this study were 1, 5, 15, and 100 ppm. No appreciable skin reactions were observed in individuals at any concentration. Three of the five concentrations evaluated were above the highest measured concentration of MCHM in the tap water of residents in West Virginia (3.7 ppm). The results of this study suggest that crude MCHM would not be a dermal irritant for the vast majority, if not all, potentially exposed persons at the concentrations in the water reported after the spill.


Assuntos
Cicloexanos/toxicidade , Pele/efeitos dos fármacos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes do Emplastro , Adulto Jovem
19.
Disaster Med Public Health Prep ; 11(5): 621-624, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28260560

RESUMO

In January 2014, a chemical spill of 4-methylcyclohexanemethanol and propylene glycol phenyl ethers contaminated the potable water supply of approximately 300,000 West Virginia residents. To understand the spill's impact on hospital operations, we surveyed representatives from 10 hospitals in the affected area during January 2014. We found that the spill-related loss of potable water affected many aspects of hospital patient care (eg, surgery, endoscopy, hemodialysis, and infection control of Clostridium difficile). Hospital emergency preparedness planning could be enhanced by specifying alternative sources of potable water sufficient for hemodialysis, C. difficile infection control, and hospital processing and cleaning needs (in addition to drinking water). (Disaster Med Public Health Preparedness. 2017;11:621-624).


Assuntos
Vazamento de Resíduos Químicos , Água Potável/normas , Serviços de Saúde/provisão & distribução , Indústria Química/normas , Cicloexanos/toxicidade , Água Potável/química , Serviços de Saúde/tendências , Humanos , Propilenoglicol/toxicidade , Rios/química , Inquéritos e Questionários , Poluição Química da Água/efeitos adversos , Abastecimento de Água/normas , West Virginia
20.
Environ Monit Assess ; 189(4): 190, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28357716

RESUMO

Thousands of gallons of industrial chemicals, crude 4-methylcyclohexanemethanol (MCHM) and propylene glycol phenyl ether (PPh), leaked from industrial tanks into the Elk River in Charleston, West Virginia, USA, on January 9, 2014. A considerable number of people were reported to exhibit symptoms of chemical exposure and an estimated 300,000 residents were advised not to use or drink tap water. At the time of the spill, the existing toxicological data of the chemicals were limited for a full evaluation of the health risks, resulting in concern among those in the impacted regions. In this preliminary study, we assessed cell viability and plasma membrane degradation following a 24-h exposure to varying concentrations (0-1000 µM) of the two compounds, alone and in combination. Evaluation of different cell lines, HEK-293 (kidney), HepG2 (liver), H9c2 (heart), and GT1-7 (brain), provided insight regarding altered cellular responses in varying organ systems. Single exposure to MCHM or PPh did not affect cell viability, except at doses much higher than the estimated exposure levels. Certain co-exposures significantly reduced metabolic activity and increased plasma membrane degradation in GT1-7, HepG2, and H9c2 cells. These findings highlight the importance of examining co-exposures to fully understand the potential toxic effects.


Assuntos
Cicloexanos/toxicidade , Éteres Fenílicos/toxicidade , Propilenoglicóis/toxicidade , Poluentes Químicos da Água/toxicidade , Linhagem Celular , Monitoramento Ambiental , Células HEK293 , Humanos , Rios/química , West Virginia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA