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1.
Artigo em Inglês | MEDLINE | ID: mdl-34477495

RESUMO

Residues of ethylene oxide (EO), a banned fumigant in the EU, were found at amounts above the maximum residue limit (MRL) in carob (locust) bean gum (additive E410). The pesticide entered the food chain via stabiliser blends that are used as minor ingredients in the manufacture of ice cream. Consequently, all products that contained the non-compliant ingredient were withdrawn or recalled in several countries across the EU, in most cases irrespective of whether the pesticide residue was detectable or not in the final product. This is the first report of a reliable method to determine EO and its metabolite/marker compound 2-chloroethanol (2-CE), either together or independently in ice cream, with a limit of quantification at 0.01 mg EO/kg and recovery in the range of 87-104% across the levels investigated (0.01, 0.02 and 0.06 mg EO/kg). The method applies QuEChERS extraction and isotope dilution gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). High resolution mass spectrometry (HRMS) confirmed the specificity of low mass ions. Data on the stability of EO and 2-CE under thermal conditions revealed that 2-CE is relatively stable in an ice cream matrix (ca. 80% recovery of spiked material). Importantly, this study also demonstrates that not EO, but 2-CE is the predominant analyte detected in the contaminated samples, which is new information of significance in terms of the overall risk assessment of EO in foodstuffs.


Assuntos
Etilenocloroidrina/análise , Óxido de Etileno/análise , Análise de Alimentos , Contaminação de Alimentos/análise , Galactanos/química , Sorvetes/análise , Mananas/química , Gomas Vegetais/química , Cromatografia Gasosa-Espectrometria de Massas
2.
Food Chem Toxicol ; 157: 112550, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34517076

RESUMO

The synthetic organic chemical, 1,2-dichloroethane (1,2-DCE), can cause brain edemas under subacute poisoning. Our previous studies indicated that neuroinflammation could be induced due to astrocytes and microglia activation during brain edemas in 1,2-DCE-intoxicated mice. However, the crosstalk between these two glial cells in 1,2-DCE-induced neuroinflammation remained unclear. In this study, primary cultured rat astrocytes and microglia, as well as an immortalized microglia cell line were employed to study the effects of 2-chloroethanol (2-CE, a 1,2-DCE intermediate metabolite in vivo) treated astrocytes on microglia polarization. Our current results revealed that 2-CE treated rat astrocytes were activated through p38 mitogen-activated protein kinase (p38 MAPK)/nuclear factor-κB (NF-κB), and activator protein-1 (AP-1) signaling pathways. Theses pathways were triggered by reactive oxygen species (ROS) produced during 2-CE metabolism. Also, astrocytes were more sensitive to 2-CE effects than microglia. Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS) expressions were upregulated in 2-CE-induced reactive astrocytes, enhancing IL-1ß, TNF-α, and nitric oxide (NO) excretions, which stimulated microglia polarization. Therefore, the neuroinflammation induced by 1,2-DCE in mice's brains is probably triggered by reactive astrocytes.


Assuntos
Astrócitos/efeitos dos fármacos , Etilenocloroidrina/farmacologia , Interleucina-1beta/metabolismo , Microglia/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Astrócitos/metabolismo , Western Blotting , Polaridade Celular/efeitos dos fármacos , Imunofluorescência , Microglia/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos
3.
J Occup Health ; 62(1): e12142, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32799435

RESUMO

OBJECTIVES: Occupational exposure to trichloroethylene (TCE) induces trichloroethylene hypersensitivity syndrome (TCEHS), which causes hypersensitivity dermatitis and hepatitis. However, whether TCE itself or its two metabolites, trichloroethanol (TCEOH) and trichloroacetic acid (TCA), are involved in TCEHS remains unclear. Therefore, in this study we explored the allergens causing TCEHS and characterized TCEHS-related liver injury in guinea pigs. METHOD: The guinea pig maximization test was performed using TCE, TCEOH, and TCA as candidate allergens. Skin inflammation was scored, and liver function and histopathological changes were evaluated by biochemical tests and hematoxylin and eosin staining, respectively. RESULTS: The sensitization rates for TCE, TCEOH, and TCA were 90.0%, 50.0%, and 0.0%, respectively. In the TCE and TCEOH experimental groups, the skin showed varying degrees of erythema with eosinophil granulocyte infiltration in the dermis. Additionally, serum alanine aminotransferase and γ-glutamyl transpeptidase levels increased significantly, and histological analysis revealed focal hepatocellular necrosis with inflammatory cell infiltration in the liver. CONCLUSIONS: TCE is the main cause of allergy and TCEOH is a secondary factor for allergy in guinea pigs. TCE and TCEOH can cause immune-mediated skin sensitization complicated by focal hepatic necrosis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Etilenocloroidrina/análogos & derivados , Necrose/induzido quimicamente , Dermatopatias/induzido quimicamente , Ácido Tricloroacético/toxicidade , Tricloroetileno/toxicidade , Animais , Etilenocloroidrina/toxicidade , Feminino , Cobaias , Hipersensibilidade/etiologia , Exposição Ocupacional
4.
Environ Sci Process Impacts ; 22(3): 719-727, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31970349

RESUMO

Smog chamber/FTIR techniques were used to investigate the kinetics and mechanism of the Cl atom and OH radical initiated oxidation of 2,2-dichloroethanol at (296 ± 1) K. Relative rate methods were used to measure k(Cl + CHCl2CH2OH) = (5.87 ± 0.96) × 10-12 and k(OH + CHCl2CH2OH) = (5.54 ± 1.94) × 10-13 cm3 molecule-1 s-1. Chlorine atom initiated oxidation of CHCl2CH2OH in one atmosphere of air gives HCOCl, CHCl2CHO, and COCl2 in yields of (62 ± 5)%, (39 ± 10)%, and (8 ± 2)%, respectively. The rate constant k(Cl + CHCl2CHO) = (8.3 ± 16) × 10-12 cm3 molecule-1 s-1 was determined and the IR spectra of CHCl2CHO is reported for the first time. The atmospheric lifetime for CHCl2CH2OH is estimated as 21 days. The experimental results are discussed in the context of the atmospheric chemistry of chlorinated alcohols.


Assuntos
Cloro , Etilenocloroidrina/análogos & derivados , Radical Hidroxila , Atmosfera , Etilenocloroidrina/química , Cinética
5.
Neurotoxicology ; 75: 233-244, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31585129

RESUMO

Brain edema caused by subacute poisoning with 1,2-dichloroethane (1,2-DCE) has gained much attention during recent years, but its underlying mechanism is poorly understood. As an intermediate metabolite of 1,2-DCE in vivo, 2-chloroethanol (2-CE) can be transformed into chloroacetaldehyde and reactive oxygen species (ROS) through cytochrome P450 2E1 (CYP2E1) mediated metabolism. In previous studies, it was found that CYP2E1 expression is enhanced in the brain of mice treated with 1,2-DCE. This study was designed to verify the roles of CYP2E1 overexpression in 2-CE induced cytotoxicity in rat astrocytes, and the contribution of specific signaling molecules to the upregulation of CYP2E1 expression caused by 2-CE. The results of this study demonstrate that treatment with 2-CE can enhance CYP2E1 protein and mRNA levels, cause an increase in ROS and MDA levels, and higher percentages of apoptotic cells in rat astrocytes. Pretreatment with either diallyl sulfide or vitamin C, the inhibitor of CYP2E1 or scavenger of ROS, respectively, can suppress the levels of CYP2E1 expression, ROS and MDA, ameliorate cell apoptosis, and attenuate phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in these cells. Additionally, pretreatment with the inhibitor of either ERK1/2 or transcriptional factor specificity protein 1 (SP1) can suppress the CYP2E1 expression, and alleviate the oxidative damage caused to these cells. In conclusion, our findings demonstrate that CYP2E1 overexpression plays a crucial role in 2-CE induced oxidative damage of rat astrocytes, and that CYP2E1 expression is upregulated partially through the activation of the ERK1/2 and SP1 signaling pathways by ROS generated during CYP2E1-mediated 2-CE metabolism. This study provides novel information that can be used in elucidating the mechanism by which 1,2-DCE induces brain edema.


Assuntos
Astrócitos/efeitos dos fármacos , Citocromo P-450 CYP2E1/metabolismo , Etilenocloroidrina/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Astrócitos/enzimologia , Astrócitos/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Imunofluorescência , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Regulação para Cima
6.
Sci Rep ; 9(1): 13923, 2019 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-31558752

RESUMO

The incorporation of 2,2,2-trichloroethanol in polyacrylamide gels allows for fluorescent visualization of proteins following electrophoresis. Ultraviolet-light exposure, in the presence of this trichlorinated compound, results in a covalent modification of the tryptophan indole ring that shifts the fluorescent emission into the visible range. Based on this principle, we used 2,2,2-trichloroethanol to develop a microplate format protein quantification assay based on the fluorescent signal generated by modified proteins. We also demonstrated a specific fluorescent emission of 2,2,2-trichloroethanol-labeled protein at 450 nm, with a 310 nm excitation, resulting from modification of both tryptophan and tyrosine residues. Following optimization, this protein quantification assay displayed superior sensitivity when compared to UV absorbance at 280 nm (A280), and enabled quantification beyond the linear range permitted by the Bradford method. This 100 µL assay displayed a sensitivity of 10.5 µg in a range up to at least 200 µg. Furthermore, we extended the utility of this method through the development of a 20 µL low-volume assay, with a sensitivity of 8.7 µg tested up to 100 µg, which enabled visualization of proteins following SDS-PAGE. Collectively, these results demonstrate the utility of 2,2,2-trichloroethanol-based protein quantification and demonstrates the protein visualization in polyacrylamide gels based on 2,2,2-trichloroethanol-labeling pre-electrophoresis.


Assuntos
Eletroforese em Gel de Poliacrilamida/métodos , Etilenocloroidrina/análogos & derivados , Proteômica/métodos , Raios Ultravioleta , Absorção de Radiação , Etilenocloroidrina/química , Proteínas/química , Triptofano/química , Tirosina/química
7.
Sci Rep ; 9(1): 9294, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31243319

RESUMO

Triclofos sodium (TCS) and chloral hydrate (CH) are widely used as sedatives for children, but no analytical method to simultaneously monitor concentrations of blood TCS, CH and their metabolites, trichloroacetic acid (TCA) and trichloroethanol (TCEOH), has been reported. The present study aimed to develop a simple analytical method for TCS and its metabolites (TCA, TCEOH and CH) in small-volume plasma from children. After acidification of specimens, TCS formic acid adduct or the metabolites derivatized using water/sulfuric acid/methanol (6:5:1, v/v) were measured by combined use of liquid chromatography tandem-mass spectrometry and gas chromatography mass-spectrometry. The limits of detection and quantification levels (µg/ml) were 0.10 and 0.29 for TCS, 0.24 and 0.72 for TCA, 0.10 and 0.31 for TCEOH, and 0.25 and 0.76 for CH, respectively. The mean recoveries were 82.8-107% for TCS, 85.4-101% for TCA, 91.6-107% for TCEOH, and 88.9-109% for CH. Within-run and between-run precision (percent of relative standard deviation, %RSD) using this method ranged from 1.1 to 15.7% and 3.6 to 13.5%, respectively, for TCS and all of its metabolites. The calibration curves were obtained with standard spiked plasma, and all of the coefficients of determination were more than 0.975. Subsequently, we applied the present method to plasma taken from five children after sedation induced by CH and TCS. In addition to TCS and CH, elevated TCA and TCEOH concentrations were detected. This new method can be applied for the pharmacokinetic analysis of TCS and its metabolites and the determination of the optimal TCS dosage in children.


Assuntos
Cromatografia Líquida/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Organofosfatos/sangue , Espectrometria de Massas em Tandem/métodos , Pré-Escolar , Hidrato de Cloral/sangue , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/sangue , Feminino , Humanos , Hidrólise , Hipnóticos e Sedativos/sangue , Lactente , Japão , Limite de Detecção , Masculino , Espectrometria de Massas , Reprodutibilidade dos Testes , Ácido Tricloroacético/sangue
8.
Sci Rep ; 9(1): 873, 2019 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-30696868

RESUMO

Because of its association with severe gastric pathologies, including gastric cancer, Helicobacter pylori has been subject of research for more than 30 years. Its capacity to adapt and survive in the human stomach can be attributed to its genetic flexibility. Its natural competence and its capacity to turn genes on and off allows H. pylori to adapt rapidly to the changing conditions of its host. Because of its genetic variability, it is difficult to establish the uniqueness of each strain obtained from a human host. The methods considered to-date to deliver the best result for differentiation of strains are Rapid Amplification of Polymorphic DNA (RAPD), Multilocus Sequence Typing (MLST) and Whole Genome Sequencing (WGS) analysis. While RAPD analysis is cost-effective, it requires a stable genome for its reliability. MLST and WGS are optimal for strain identification, however, they require analysis of data at the bioinformatics level. Using the StainFree method, which modifies tryptophan residues on proteins using 2, 2, 2, - trichloroethanol (TCE), we observed a strain specific pattern of tryptophan in 1D acrylamide gels. In order to establish the effectiveness of tryptophan fingerprinting for strain identification, we compared the graphic analysis of tryptophan-labelled bands in the gel images with MLST results. Based on this, we find that tryptophan banding patterns can be used as an alternative method for the differentiation of H. pylori strains. Furthermore, investigating the origin for these differences, we found that H. pylori strains alters the number and/or position of tryptophan present in several proteins at the genetic code level, with most exchanges taking place in membrane- and cation-binding proteins, which could be part of a novel response of H. pylori to host adaptation.


Assuntos
Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Triptofano/metabolismo , DNA Bacteriano/genética , Etilenocloroidrina/análogos & derivados , Genoma Bacteriano/genética , Genótipo , Infecções por Helicobacter/genética , Humanos , Tipagem de Sequências Multilocus/métodos , Técnica de Amplificação ao Acaso de DNA Polimórfico/métodos , Reprodutibilidade dos Testes , Análise de Sequência de DNA/métodos , Neoplasias Gástricas/genética
9.
Methods Mol Biol ; 1853: 179-190, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30097944

RESUMO

SDS-polyacrylamide gel electrophoresis (SDS-PAGE) is one of the essential techniques in molecular biology and biochemistry laboratories and requires rapid visualization methods for efficient sample analysis. Proteins on polyacrylamide gels can be visualized within 5 min via the photoreaction of tryptophan with trichloroethanol. This process does not require protein fixation, staining, or destaining. In this method polyacrylamide gels are prepared by adding trichloroethanol before polymerization. After electrophoresis, the gel is immediately activated on a standard UV transilluminator and the fluorescently labeled proteins are imaged. The reaction is based on the photoreaction of trichloroethanol with tryptophan residues within the protein. This generates a visible blue-green fluorescence (∼500 nm) that is accurately imaged. Here we describe the preparation of Tris-glycine and Tris-tricine SDS-polyacrylamide gels with trichloroethanol and the photoreaction and visualization of tryptophan containing proteins.


Assuntos
Eletroforese em Gel de Poliacrilamida , Etilenocloroidrina/análogos & derivados , Proteínas Luminescentes , Fotoquímica , Triptofano , Eletroforese em Gel de Poliacrilamida/métodos , Etilenocloroidrina/química , Proteínas Luminescentes/análise , Proteínas Luminescentes/química , Fotoquímica/métodos , Triptofano/química
10.
Acta Crystallogr F Struct Biol Commun ; 74(Pt 5): 307-314, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29717999

RESUMO

The identification of initial lead conditions for successful protein crystallization is crucial for structural studies using X-ray crystallography. In order to reduce the number of false-negative conditions, an emerging number of fluorescence-based methods have been developed which allow more efficient identification of protein crystals and help to distinguish them from salt crystals. Detection of the native tryptophan fluorescence of protein crystals is one of the most widely used methods. However, this method can fail owing to the properties of the crystallized protein or the chemical composition of the crystallization trials. Here, a simple, fast and cost-efficient method employing 2,2,2-trichloroethanol (TCE) has been developed. It can be performed with a standard UV-light microscope and can be applied to cases in which detection of native tryptophan fluorescence fails. In four test cases this method had no effect on the diffraction properties of the crystals and no structural changes were observed. Further evidence is provided that TCE can be added to crystallization trials during their preparation, making this method compatible with high-throughput approaches.


Assuntos
Etilenocloroidrina/análogos & derivados , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Etilenocloroidrina/metabolismo , Microscopia de Fluorescência/métodos , Estrutura Secundária de Proteína
11.
J Biomol Struct Dyn ; 36(3): 551-560, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28150569

RESUMO

Catalase, a ubiquitous enzyme of the free radical scavenging machinery unfolds and aggregates in the presence of 2,2,2-triflouroethanol (TFE). Catalase molecule aggregates at 50% TFE as evident by high thioflavin T fluorescence, shifted congo red absorbance, change in circular dichroism and soret spectra. TEM images confirmed the nature of catalase aggregates to be oligomers. Organic solvent-induced aggregation of catalase is prevented by the presence of peroxidase (another enzyme of the free radical scavenging machinery). To alter the progress of aggregation in presence of increasing concentration of TFE, we determined the effect of peroxidase on catalase oligomerization by several different techniques, including turbidity measurement, activity assay, thioflavin T fluorescence, circular dichroism, shift in congo red absorbance, transmission electron microscopy (TEM), Rayleigh scattering, soret absorption spectra, and ANS fluorescence. The presence of peroxidase in the vicinity of folded catalase helps it to remain functionally active and inhibited aggregation in the presence of TFE, suggesting that proteins are stable in crowded environments. Moreover, this catalase-peroxidase interaction is biologically significant as it provides insights into how the aggregation process may be altered.


Assuntos
Catalase/química , Peroxidase/química , Agregados Proteicos/efeitos dos fármacos , Multimerização Proteica/efeitos dos fármacos , Dicroísmo Circular , Vermelho Congo , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/química , Sequestradores de Radicais Livres/química , Ligação Proteica , Conformação Proteica/efeitos dos fármacos , Desnaturação Proteica , Dobramento de Proteína , Espectrometria de Fluorescência
12.
Anal Biochem ; 521: 8-10, 2017 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-28069453

RESUMO

Gelatinase zymography is a commonly used laboratory procedure; however, variability in sample loading and concentration reduce the accuracy of quantitative results obtained from this technique. To facilitate normalization of gelatinase activity by loaded protein amount, we developed a protocol using the trihalocompound 2,2,2-trichloroethanol to allow for gelatin zymography and total protein labeling within the same gel. We showed that detected protein levels increased linearly with loading, and describe a loading concentration range over which normalized gelatinase activity was constant. We conclude that in-gel total protein detection is feasible in gelatin zymography and greatly improves comparison of gelatinase activity between samples.


Assuntos
Eletroforese em Gel de Poliacrilamida/normas , Fibrossarcoma/enzimologia , Gelatina/metabolismo , Gelatinases/metabolismo , Metaloproteinases da Matriz/análise , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/metabolismo , Humanos , Metaloproteinases da Matriz/metabolismo , Células Tumorais Cultivadas
13.
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi ; 35(10): 780-782, 2017 Oct 20.
Artigo em Chinês | MEDLINE | ID: mdl-29294559

RESUMO

Objective: To establish a method for determing the trichloroethylene(TCE)and trichloroethanol(TCOH)in blood samples by liquid-liquid extraction-gas chromatography with electron capture detector. Methods: With this method,ether was used as extraction solvent and trichloromethane was used as an internal standard. The whole blood sample was extracted with ether, and dehydrated by anhydrous sodium sulfate. Then the analytes were separated on HP-5 capillary column(30m×0.32mm×0.15µm)and detected byECD.The retention time was for qualitative analysis and the internal standard was for quantitation. Results: The standard curves of TCE and TCOH showed significant linearity between 95.5µg/L-7640.0µg/L(r=0.9997)and 19.0µg/L-1520.0µg/L(r=0.9992). The average recovery was 95.5%-103.6%.The intra-day and inter-day precisions(RSD)were 2.5%-6.8%(n=6)and 1.6%-4.3%(n=6) respectively. The detect limit of TCE and TCOH were 2.10 µg/L and 0.56µg/L(S/N=3)respectively.The blood can be kept 7 days at-20℃ refrigerator without significantly loss. Conclusion: This method is proved to be simple,practical and highly sensitive. It can satisfy the request for the determination of blood samples of humans exposed to TCE.


Assuntos
Cromatografia Gasosa/métodos , Etilenocloroidrina/análogos & derivados , Extração Líquido-Líquido/métodos , Tricloroetileno/sangue , Etilenocloroidrina/sangue , Humanos
14.
Biochem Mol Biol Educ ; 43(5): 358-65, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26153352

RESUMO

SDS-PAGE and western blotting are two commonly taught protein detection techniques in biochemistry and molecular biology laboratory classrooms. A pitfall associated with incorporating these techniques into the laboratory is the significant wait times that do not allow students to obtain timely results. The waiting associated with SDS-PAGE comes from staining and destaining, whereas with western blotting it is the times required for antibody incubations and the numerous wash steps. This laboratory exercise incorporates 2,2,2-trichloroethanol (TCE) into the SDS-PAGE gel allowing for visualization of migrated proteins in a matter of minutes, saving both the time and chemical waste associated with traditional Coomassie staining. Additionally, TCE staining does not affect protein transfer eliminating the requirement for duplicated gels for total protein and western analyses. Protein transfer can be confirmed immediately without the use of Ponceau S staining. Lastly, this western blot procedure has been further shortened by using an HRP-conjugated primary antibody, which eliminates the secondary antibody incubation and washes, and uses a colorimetric detection to allow for visualization by students without the need for specialized equipment.


Assuntos
Western Blotting/métodos , Educação/métodos , Biologia Molecular/educação , Currículo , Eletroforese em Gel de Poliacrilamida/métodos , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/química , Peroxidase do Rábano Silvestre/química , Humanos , Laboratórios , Biologia Molecular/métodos , Estudantes , Universidades
15.
J Toxicol Environ Health A ; 78(11): 671-84, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26039745

RESUMO

It was recently demonstrated that some drugs modulate in vitro metabolism of trichloroethylene (TCE) in humans and rats. The objective was to assess in vivo interactions between TCE and three drugs: naproxen (NA), valproic acid (VA), and salicylic acid (SA). Animals were exposed to TCE by inhalation (50 ppm for 6 h) and administered a bolus dose of drug by gavage, equivalent to 10-fold greater than the recommended daily dose. Samples of blood, urine, and collected tissues were analyzed by headspace gas chromatography coupled to an electron capture detector for TCE and metabolites (trichloroethanol [TCOH] and trichloroacetate [TCA]) levels. Coexposure to NA and TCE significantly increased (up to 50%) total and free TCOH (TCOHtotal and TCOHfree, respectively) in blood. This modulation may be explained by an inhibition of glucuronidation. VA significantly elevated TCE levels in blood (up to 50%) with a marked effect on TCOHtotal excretion in urine but not in blood. In contrast, SA produced an increase in TCOHtotal levels in blood at 30, 60, and 90 min and urine after coexposure. Data confirm in vitro observations that NA, VA, and SA affect in vivo TCE kinetics. Future efforts need to be directed to evaluate whether populations chronically medicated with the considered drugs display greater health risks related to TCE exposure.


Assuntos
Etilenocloroidrina/análogos & derivados , Naproxeno/metabolismo , Ácido Salicílico/metabolismo , Solventes/metabolismo , Ácido Tricloroacético/metabolismo , Tricloroetileno/metabolismo , Ácido Valproico/metabolismo , Analgésicos/metabolismo , Animais , Anti-Inflamatórios não Esteroides/metabolismo , Anticonvulsivantes/metabolismo , Etilenocloroidrina/sangue , Etilenocloroidrina/metabolismo , Etilenocloroidrina/farmacocinética , Etilenocloroidrina/urina , Masculino , Modelos Teóricos , Ratos , Ratos Sprague-Dawley , Medição de Risco , Solventes/farmacocinética , Ácido Tricloroacético/sangue , Ácido Tricloroacético/farmacocinética , Ácido Tricloroacético/urina , Tricloroetileno/sangue , Tricloroetileno/farmacocinética , Tricloroetileno/urina
16.
Phys Med Biol ; 60(12): 4685-704, 2015 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-26020119

RESUMO

In this study, recipe optimization of Leuco Crystal Violet (LCV) micelle gels made with the surfactant Cetyl Trimethyl Ammonium Bromide (CTAB) and the chemical sensitizer 2,2,2-trichloroethanol (TCE) was aided by a two-level three-factor designed experiment. The optimized recipe contains 0.75 mM LCV, 17.0 mM CTAB, 120 mM TCE, 25.0 mM tri-chloro acetic acid (TCAA), 4 wt% gelatin and ~96 wt% water. Dose sensitivity of the optimized gel is 1.5 times higher than that of Jordan's standard LCV micelle gel. Spatial integrity of the 3D dose distribution information in 1L phantoms filled with this recipe is maintained for >120 d. Unfortunately, phantoms made using the optimized recipe showed dose-rate dependence (14% difference in optical attenuation at the peak dose using electron beam irradiations at 100 and 400 MU min(-1)). Further testing suggests that the surfactant CTAB is the cause of this dose rate behaviour.


Assuntos
Géis/química , Violeta Genciana/química , Imagens de Fantasmas , Radiometria/métodos , Radiometria/normas , Tensoativos/química , Água/química , Cetrimônio , Compostos de Cetrimônio/química , Relação Dose-Resposta à Radiação , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/química , Micelas
17.
Phys Med Biol ; 60(12): 4665-83, 2015 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-26020840

RESUMO

Radiochromic leuco crystal violet (LCV) micelle gel dosimeters are promising three-dimensional radiation dosimeters because of their spatial stability and suitability for optical readout. The effects of surfactant type and surfactant concentration on dose sensitivity of LCV micelle gels are tested, demonstrating that dose sensitivity and initial colour of the gel increases with increasing Triton x-100 (Tx100) concentration. Using Cetyl Trimethyl Ammonium Bromide (CTAB) in place of Tx100 produces gels that are nearly colourless prior to irradiation, but reduces the dose sensitivity. The separate effects of Tri-chloro acetic acid concentration and pH are investigated, revealing that controlling the pH near 3.6 is crucial for achieving high dose sensitivity. The sensitizing effect of chlorinated species on dose sensitivity is tested using 2,2,2-trichloroethanol (TCE), chloroform, and 1,1,1-trichloro-2-methyl-2-propanol hemihydrate. TCE gives the largest improvement in dose sensitivity and is recommended for use in micelle gel dosimeters because it is less volatile and safer to use than chloroform. Preliminary experiments on a new gel containing CTAB as the surfactant and TCE show that this new gel gives a dose sensitivity that is 24% higher than that of previous LCV micelle gels and is nearly colourless prior to irradiation.


Assuntos
Géis/química , Violeta Genciana/química , Radiometria/métodos , Corantes de Rosanilina/química , Tensoativos/química , Cetrimônio , Compostos de Cetrimônio/química , Relação Dose-Resposta à Radiação , Etilenocloroidrina/análogos & derivados , Etilenocloroidrina/química , Concentração de Íons de Hidrogênio , Micelas , Octoxinol/química , Ácido Tricloroacético/química
18.
Org Lett ; 17(10): 2396-9, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25941891

RESUMO

The first organocatalytic enantioselective oxidative C-H functionalization of N-acyl tetrahydroisoquinolines with vinyl and aryl boronates promoted by a chiral Brønsted acid is described. This metal-free process tolerates a wide range of electronically varied N-acyl tetrahydroisoquinolines and structurally diverse boronates with good to excellent enantioselectivities.


Assuntos
Ácidos Borônicos/química , Etilenocloroidrina/análogos & derivados , Tetra-Hidroisoquinolinas/química , Trifluoretanol/química , Catálise , Etilenocloroidrina/química , Estrutura Molecular , Estereoisomerismo
19.
Biochem Biophys Res Commun ; 462(3): 239-44, 2015 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-25956065

RESUMO

2,2,2-Trichloroethanol (TCOH) is responsible for the pharmacological actions of chloral hydrate (CH), and is a major metabolite of trichloroethylene. Human exposure to TCOH is known to be increasing. Recently, it was reported that TCOH causes a significant phase delay of Per2 expression in mouse liver when injected daily over the course of several days. However, it is not clear whether TCOH directly modulates the molecular clock. In the present study we used a cell-based assay system to test this possibility. We found that the daily oscillation period of Bmal1 was lengthened to 3 h following treatment with 1.5 mM TCOH, and increased to 5 h with 3 mM TCOH treatment. However, low concentrations of TCOH had no noticeable effects. The effect of TCOH on Per2 oscillation was marginal. Interestingly, serum from rats anesthetized with CH also modulated Bmal1 period, suggesting that exposure to anesthesia should be taken into consideration for circadian rhythm studies. In summary, our study reveals a direct regulation of TCOH on molecular clock.


Assuntos
Fatores de Transcrição ARNTL/genética , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/genética , Etilenocloroidrina/análogos & derivados , Animais , Proteínas CLOCK/genética , Linhagem Celular , Hidrato de Cloral/farmacologia , Hidrato de Cloral/toxicidade , Etilenocloroidrina/farmacologia , Etilenocloroidrina/toxicidade , Humanos , Hipnóticos e Sedativos/farmacologia , Hipnóticos e Sedativos/toxicidade , Medições Luminescentes , Masculino , Camundongos , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Proteínas Circadianas Period/genética , Ratos , Ratos Endogâmicos F344
20.
J Appl Toxicol ; 35(3): 295-301, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25345596

RESUMO

A number of recent reports suspected that Tween-80 in injectable medicines, including traditional Chinese medicine injections could cause life-threatening anaphylactoid reaction, but no sound conclusion was drawn. A drug-induced anaphylactoid reaction is hard to be assayed in vitro and in conventional animal models. In this study, we developed a microplate-based quantitative in vivo zebrafish assay for assessing anaphylactoid reaction and live whole zebrafish mast cell tryptase activity was quantitatively measured at a wavelength of 405 nm using N-benzoyl-dl-arginine p-nitroanilide as a substrate. We assessed 10 batches of Tween-80 solutions from various national and international suppliers and three Tween-80 impurities (ethylene glycol, 2-chloroethanol and hydrogen peroxide) in this model and found that three batches of Tween-80 (nos 2, 20080709 and 20080616) and one Tween-80 impurity, hydrogen peroxide (H2 O2 ), induced anaphylactoid reactions in zebrafish. Furthermore, we found that H2 O2 residue and peroxide value were much higher in Tween-80 samples 2, 20080709 and 20080616. These findings suggest that H2 O2 residue in combination with oxidized fatty acid residues (measured as peroxide value) or more likely the oxidized fatty acid residues in Tween-80 samples, but not Tween-80 itself, may induce anaphylactoid reaction. High-throughput zebrafish tryptase assay developed in this report could be used for assessing safety of Tween-80-containing injectable medicines and potentially for screening novel mast cell-modulating drugs.


Assuntos
Anafilaxia/induzido quimicamente , Contaminação de Medicamentos , Excipientes/toxicidade , Polissorbatos/toxicidade , Peixe-Zebra/imunologia , Anafilaxia/enzimologia , Anafilaxia/imunologia , Animais , Medicamentos de Ervas Chinesas/administração & dosagem , Etilenocloroidrina/química , Etilenocloroidrina/toxicidade , Etilenoglicol/química , Etilenoglicol/toxicidade , Excipientes/química , Ensaios de Triagem em Larga Escala , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/toxicidade , Intestinos/efeitos dos fármacos , Mastócitos/efeitos dos fármacos , Polissorbatos/química , Triptases/metabolismo
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