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1.
Analyst ; 146(18): 5658-5667, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34382628

RESUMO

With the rapid development of various industries, cyanide (CN-) and hypochlorite (ClO-) have a tremendously adverse effect on the health of humans and animals. In this study, a fluorescent probe HHTB based on a benzaldehyde-indole fused chromophore was designed to detect cyanide and hypochlorite simultaneously. The synthesized probe was found to have strong anti-interference ability. In addition, the designed probe could respond rapidly to ClO- in just 80 s, while the color changed visibly from red to colorless. Moreover, the response time to CN- was longer (about 160 s), with the apparent color change from red to light red. The ratiometric and colorimetric absorbance variation of HHTB was due to the nucleophilic attack of CN- on the indole CN functional group and the strong oxidization of ClO- which destroyed the CC bonds and the conjugation systems. Furthermore, the probe HHTB responding to ClO- and CN- presented high sensitivity, as the calculated detection limits were 1.18 nM and 1.40 nM, respectively. The probe was also found to have low biological toxicity and was used in living cells successfully. Therefore, it has good application prospect in the field of cell imaging and biomedicine. The binding mechanism of HHTB-CN and the reaction mechanism of HHTB and ClO- were further elucidated by a series of experiments.


Assuntos
Corantes Fluorescentes , Ácido Hipocloroso , Animais , Benzaldeídos/toxicidade , Cianetos/toxicidade , Corantes Fluorescentes/toxicidade , Humanos , Ácido Hipocloroso/toxicidade , Indóis/toxicidade
2.
Toxicol Lett ; 349: 30-39, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34089818

RESUMO

The global descriptors of chemical activity: ionization potential IP, electron affinity EA, chemical potential µ, absolute electronegativity χ, molecular hardness η and softness S, electrophilicity index ω for cyanides X(CN)k with X=H, Na, K, Ag, Cu, Ca, Hg, Cd, Zn in the gas phase and water medium have been determined by taking advantage of the quantum-chemical computations. To this aim, the HOMO and LUMO energy levels were calculated using DFT B3LYP method and QZVP (Valence Quadruple-Zeta Polarization) basis set, which enables precise calculations for hydrogen cyanide and its salts containing both light (H, Na, Ca) and heavy (K, Ag, Cu, Cd, Hg, Zn) atoms. The results obtained indicate that while the EA-parameter roughly determines the LD50 values for the cyanides considered, the ω-descriptor is related rather to the product of cyanide LD50 and hydrolysis n-degree. Hence, the theoretical LD50CN(ω) function proposed is interconnected with the n⸳LD50 collective variable, whereas LD50(EA) directly approximates LD50 values indicating that the toxicity of cyanides decreases with increasing EA, ω-values. The calculations carried out suggest that some of the LD50(Exp) experimentally determined are incorrect (AgCN) or inaccurate (Cd(CN)2) and require revision. Comparison of the theoretically estimated LD50(ω) with NOAEL toxicity parameters indicates that they are well correlated ​​in contrast to LD50(EA)​​ and LD50(Exp),​​ exhibiting lower and marginal degrees of correlation, respectively.


Assuntos
Cianetos/toxicidade , Modelos Moleculares , Testes de Toxicidade , Animais , Cianetos/química , Relação Dose-Resposta a Droga , Humanos , Dose Letal Mediana , Estrutura Molecular , Nível de Efeito Adverso não Observado , Medição de Risco , Relação Estrutura-Atividade
3.
J Med Toxicol ; 17(3): 257-264, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33821433

RESUMO

INTRODUCTION: Cyanide is a deadly poison, particularly with oral exposure where larger doses can occur before symptoms develop. Prior studies and multiple governmentagencies highlight oral cyanide as an agent with the potential for use in a terrorist attack. Currently, there are no FDA approved antidotes specific to oralcyanide. An oral countermeasure that can neutralize and prevent absorption of cyanide from the GI tract after oral exposure is needed. Our objective was toevaluate the efficacy of oral sodium thiosulfate on survival and clinical outcomes in a large, swine model of severe cyanide toxicity. METHODS: Swine (45-55kg) were instrumented, sedated, and stabilized. Potassium cyanide (8 mg/kg KCN) in saline was delivered as a one-time bolus via an orogastric tube. Three minutes after cyanide, animals randomized to the treatment group received sodium thiosulfate (510 mg/kg, 3.25 M solution) via orogastric tube. Our primary outcome was survival at 60 minutes after exposure. We compared survival between groups by log-rank, Mantel-Cox analysis and trended labs and vital signs. RESULTS: At baseline and time of treatment all animals had similar weights, vital signs, and laboratory values. Survival at 60 min was 100% in treated animals compared to 0% in the control group (p=0.0027). Animals in the control group became apneic and subsequently died by 35.0 min (20.2,48.5) after cyanide exposure. Mean arterial pressure was significantly higher in the treatment group compared to controls (p=0.008). Blood lactate (p=0.02) and oxygen saturation (p=0.02) were also significantly different between treatment and control groups at study end. CONCLUSION: Oral administration of sodium thiosulfate improved survival, blood pressure, respirations, and blood lactate concentrations in a large animal model of acute oral cyanide toxicity.


Assuntos
Antídotos/uso terapêutico , Cianetos/toxicidade , Tiossulfatos/uso terapêutico , Administração Oral , Animais , Humanos , Modelos Animais , Suínos , Tiossulfatos/administração & dosagem , Resultado do Tratamento
4.
Artigo em Inglês | MEDLINE | ID: mdl-33593243

RESUMO

The initial cyanide (CN-) concentration and amount of co-contaminants in GCTs can inhibit bacterial growth and reduce the CN--degrading ability of bacteria. Several microorganisms can biotransform a wide range of organic and inorganic industrial contaminants into nontoxic compounds. However, active enzymatic CN- metabolism processes are mostly constrained by the physical and chemical characteristics of GCTs. High concentrations of toxic metal co-contaminants, such as, Pb, and Cr, and factors, such as pH, temperature, and oxygen concentration create oxidative stress and limit the CN--degrading potential of cyanotrophic strains. The effects of such external and internal factors on the CN--degrading ability of bacteria hinder the selection of suitable microorganisms for CN- biodegradation. Therefore, understanding the effects of the physicochemical properties of GCTs on cyanobacteria strains can help identify suitable microbes and favorable environmental conditions to promote microbial growth and can also help design efficient CN- biodegradation processes. In this review, we present a detailed analysis of the physicochemical properties of GCTs and their effects on microbial CN- degradation.


Assuntos
Cianetos/toxicidade , Cianobactérias/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Ouro/toxicidade , Biodegradação Ambiental/efeitos dos fármacos , Cianetos/química , Cianetos/metabolismo , Cianobactérias/crescimento & desenvolvimento , Cianobactérias/metabolismo , Poluentes Ambientais/química , Poluentes Ambientais/metabolismo , Ouro/química , Ouro/metabolismo , Resíduos Industriais/análise
5.
J Sci Food Agric ; 101(8): 3290-3297, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33222187

RESUMO

BACKGROUND: Ginkgo biloba seeds are used as a functional food across Asia. However, the presence of toxic compounds has limited their application. In this study, freeze drying, infrared drying, hot-air drying and pulsed-vacuum drying were used to dry G. biloba seeds. A comprehensive analysis was performed on their product quality, antioxidant activities, bioactive and toxic components. RESULTS: Results showed that the drying methods had a significant influence on product quality with freeze drying being superior due to the minimal microstructural damage, followed by infrared drying and pulsed-vacuum drying. Infrared-dried product possessed the strongest antioxidant activities and higher bioactive compound content than hot-air-dried and pulsed-vacuum-dried product. Toxic compounds in fresh G. biloba seeds (ginkgotoxin, ginkgolic acid and cyanide) were reduced markedly by drying. Ginkgotoxin was reduced fourfold, and the contents of acrylamide, ginkgolic acid and cyanide in dried G. biloba seeds were reduced to the scope of safety. Amongst the four drying methods, infrared drying had the shortest drying time, and its product showed higher quality and bioactive compound content, and stronger antioxidant activities. CONCLUSIONS: These findings will offer salient information for selecting a drying method during the processing of ginkgo seeds. Infrared drying could be considered as a multiple-effect drying method in the processing of ginkgo seeds. © 2020 Society of Chemical Industry.


Assuntos
Antioxidantes/análise , Dessecação/métodos , Manipulação de Alimentos/métodos , Ginkgo biloba/química , Sementes/química , Cianetos/análise , Cianetos/toxicidade , Dessecação/instrumentação , Manipulação de Alimentos/instrumentação , Ginkgo biloba/toxicidade , Piridoxina/análogos & derivados , Piridoxina/análise , Piridoxina/toxicidade , Controle de Qualidade , Salicilatos/análise , Sementes/toxicidade
6.
Basic Clin Pharmacol Toxicol ; 128(3): 534-541, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33090684

RESUMO

Azide is a highly toxic chemical agent to human being. Accidental, but also intentional exposure to azide occurs. To be able to confirm azide ingestion, we developed a method to identify and quantify azide in biological matrices. Cyanide was included in the method to evaluate suggested in vivo production of cyanide after azide ingestion. Azide in biological matrices was first derivatized by propionic anhydride to form propionyl azide. Simultaneously, cyanide was converted into hydrogen cyanide. After thermal rearrangement of propionyl azide, ethyl isocyanate was formed, separated together with hydrogen cyanide by gas chromatography (GC) and detected using a nitrogen phosphorous detector (NPD). The method was linear from 1.0-100 µg/mL for both analytes, and azide was stable in human plasma at -20°C for at least 49 days. Azide was measured in the gastric content of two cases of suspected azide ingestion (case 1:1.2 mg/mL, case 2:1.5 mg/mL). Cyanide was only identified in the gastric content of case 1 (approximately 1.4 µg/mL). Furthermore, azide was quantified in plasma (19 µg/mL), serum (24 µg/mL), cell pellet (21 µg/mL) and urine (3.0 µg/mL) of case 2. This method can be used to confirm azide and cyanide exposure, and azide concentrations can be quantified in several biological matrices.


Assuntos
Azidas/toxicidade , Cromatografia Gasosa/métodos , Cianetos/toxicidade , Adulto , Azidas/análise , Azidas/envenenamento , Cianetos/análise , Feminino , Humanos
7.
Oxid Med Cell Longev ; 2020: 8877100, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33144915

RESUMO

This study investigated the effect of anthracycline antibiotics, mitomycin C, and menadione on oxygen consumption and hydrogen peroxide production by intact, beating, rat heart myocytes. Doxorubicin produced a dose-dependent increase in the rate of cyanide-resistant respiration by beating myocytes. The anthracycline analogs 4-demethoxydaunorubicin, 4'-epidoxorubicin, 4'-deoxydoxorubicin, and menogaril, as well as the anticancer quinones mitomycin C and menadione, also significantly increased oxygen consumption by cardiac myocytes. However, 5-iminodaunorubicin (which has a substituted quinone group) and mitoxantrone (which is not easily reduced by flavin dehydrogenases) had no effect on cardiac respiration. Both catalase (43%) and acetylated cytochrome c (19%) significantly decreased oxygen consumption that had been stimulated by doxorubicin; furthermore, extracellular hydrogen peroxide production was increased from undetectable control levels to 1.30 ± 0.02 nmol/min/107 myocytes (n = 4, P < 0.01) in the presence of 400 µM doxorubicin. These experiments suggest that the anthracycline antibiotics and other anticancer quinones stimulate cardiac oxygen radical production in intact heart myocytes; such a free radical cascade could contribute to the cardiac toxicity of these drugs.


Assuntos
Envelhecimento/metabolismo , Antineoplásicos/farmacologia , Benzoquinonas/farmacologia , Miócitos Cardíacos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Respiração Celular/efeitos dos fármacos , Cianetos/toxicidade , Doxorrubicina/farmacologia , Sequestradores de Radicais Livres/farmacologia , Peróxido de Hidrogênio/metabolismo , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Consumo de Oxigênio/efeitos dos fármacos , Ratos Sprague-Dawley
9.
Chem Res Toxicol ; 33(11): 2834-2844, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33112595

RESUMO

Elemental mercury (Hg0) contamination in artisanal and small-scale gold mining (ASGM) communities is widespread, and Hg0-contaminated tailings are often reprocessed with cyanide (-CN) to extract residual gold remaining after amalgamation. Hg0 reacts with -CN under aerobic conditions to produce Hg(CN)42- and other Hg(CN)nn-2 complexes. The production of solvated Hg(CN)nn-2 complexes increases upon agitation in the presence of synthetic and authentic Hg0-contaminated tailings that aid in dispersing the Hg0, increasing its reactive surface area. Adult rats were exposed to various concentrations of Hg(CN)2, and accumulation in organs and tissues was quantified using direct mercury analysis. The primary site of Hg(CN)2 accumulation was the kidney, although accumulation was also detected in the liver, spleen, and blood. Little accumulation was observed in the brain, suggesting that Hg(CN)2 complexes do not cross the blood-brain barrier. Renal tissue was particularly sensitive to the effects of Hg(CN)2, with pathological changes observed at low concentrations. Hg(CN)2 complexes are handled by mammalian systems in a manner similar to other inorganic species of Hg, yet appear to be more toxic to organ systems. The findings from this study are the first to show that Hg(CN)2 complexes are highly stable complexes that can lead to cellular injury and death in mammalian organ systems.


Assuntos
Cianetos/toxicidade , Ouro/toxicidade , Compostos de Mercúrio/toxicidade , Mercúrio/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Monitoramento Ambiental , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Mineração , Ratos , Ratos Wistar , Solubilidade , Baço/efeitos dos fármacos
10.
Ecotoxicology ; 29(9): 1552-1564, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32803565

RESUMO

Exogenous cyanide (CN-) effects on nitrogen (N) uptake, transport, and assimilation in rice seedlings were investigated at the biochemical and molecular levels. Seedlings were treated with either a 2-d or 4-d supply of potassium cyanide (KCN) in the nutrient solution containing nitrate (NO3-) or ammonium (NH4+). Although a KCN-induced increase was recorded in the activity of ß-cyanoalanine synthase (ß-CAS) in rice tissues of both NH4+-fed and NO3--fed seedlings, the former showed a significantly greater assimilation rate for CN- than the latter. The addition of KCN decreased NO3- uptake and assimilation, whereas a negligible impact was observed in NH4+ treatments. Enzymatic assays showed a marked activities enhancement of glutamine synthetase (GS), glutamate synthase (GOGAT), and glutamate dehydrogenase (GDH) in NH4+-fed seedlings after KCN exposure. Similarly, the rises occurring in nitrate reductase (NR) and GDH activity in NO3--fed seedlings were also detected after 2-d exposure to KCN, whereas a significant reduction of GS and GOGAT activities was determined. The results suggest that although exogenous KCN at moderate or high concentrations caused repressively effects on biomass growth of both NH4+-fed and NO3--fed rice seedlings, the nontoxic concentration of KCN supplied can serve as a supplemental N source in plant nutrition and N metabolism.


Assuntos
Cianetos/toxicidade , Oryza/fisiologia , Compostos de Amônio , Biomassa , Cianetos/metabolismo , Glutamato-Amônia Ligase , Liases , Nitrato Redutase , Nitratos , Nitrogênio , Plântula
11.
Chemosphere ; 252: 126499, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32224356

RESUMO

Cyanide-containing organic wastewater is discharged in large quantities by coking, electroplating and pharmaceutical industries, which seriously endangers environmental safety and human health. In this paper, Electrochemical Oxidation-Persulfate (EO-PS) Advanced Oxidation Process (AOP) was firstly used to treat high concentration cyanide-containing organic wastewater obtained from a chemical enterprise. The potential application of this process in the treatment of high concentration cyanide-containing organic wastewater was explored for the first time, and the effects of current density, initial pH, temperature and initial concentration on chemical oxygen demand (COD), total organic carbon (TOC) and total cyanide (CN-) removal in wastewater were systematically investigated. The results shown that the EO-PS process had an excellent removal effect on organics and cyanide in high concentration cyanide-containing organic wastewater which contained 11,290 mg L-1 COD, 4456 mg L-1 TOC and 1280.15 mg L-1 CN-. The COD, TOC and CN- removal at optimized operating parameters for 24 h were 95.8%, 87.8% and 98.4%, respectively. The corresponding electrical energy per order was only 41.6 kWh m-3 order-1. In addition, the pollutants removal can be accelerated under conditions of high current density, acidic solution, appropriate temperature and low pollutant concentration, among which low current density, low pH, appropriate temperature and low pollutant concentration can effectively diminish energy consumption. Cyanide, COD and TOC degradation in all reaction conditions followed the pseudo-first-order kinetic model.


Assuntos
Cianetos/química , Sulfatos/química , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Poluentes Químicos da Água/química , Análise da Demanda Biológica de Oxigênio , Boro , Coque , Cianetos/toxicidade , Diamante , Eletrodos , Cinética , Oxirredução , Poluentes Químicos da Água/toxicidade
12.
Biomol Concepts ; 11(1): 32-56, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32187011

RESUMO

The inefficiency of cyanide/HCN (CN) binding with heme proteins (under physiological regimes) is demonstrated with an assessment of thermodynamics, kinetics, and inhibition constants. The acute onset of toxicity and CN's mg/Kg LD50 (µM lethal concentration) suggests that the classical hemeFe binding-based inhibition rationale is untenable to account for the toxicity of CN. In vitro mechanistic probing of CN-mediated inhibition of hemeFe reductionist systems was explored as a murburn model for mitochondrial oxidative phosphorylation (mOxPhos). The effect of CN in haloperoxidase catalyzed chlorine moiety transfer to small organics was considered as an analogous probe for phosphate group transfer in mOxPhos. Similarly, inclusion of CN in peroxidase-catalase mediated one-electron oxidation of small organics was used to explore electron transfer outcomes in mOxPhos, leading to water formation. The free energy correlations from a Hammett study and IC50/Hill slopes analyses and comparison with ligands ( CO/ H 2 S/ N 3 - ) $\left( {\text{CO}}/{{{{\text{H}}_{2}}\text{S}}/{\text{N}_{3}^{\text{-}}}\;}\; \right)$ provide insights into the involvement of diffusible radicals and proton-equilibriums, explaining analogous outcomes in mOxPhos chemistry. Further, we demonstrate that superoxide (diffusible reactive oxygen species, DROS) enables in vitro ATP synthesis from ADP+phosphate, and show that this reaction is inhibited by CN. Therefore, practically instantaneous CN ion-radical interactions with DROS in matrix catalytically disrupt mOxPhos, explaining the acute lethal effect of CN.


Assuntos
Cianetos/toxicidade , Heme/química , Hemeproteínas/antagonistas & inibidores , Hemoglobinas/antagonistas & inibidores , Mitocôndrias/efeitos dos fármacos , Trifosfato de Adenosina/biossíntese , Trifosfato de Adenosina/química , Trifosfato de Adenosina/metabolismo , Sítios de Ligação , Catalase/metabolismo , Catálise , Respiração Celular/efeitos dos fármacos , Respiração Celular/fisiologia , Cloreto Peroxidase/química , Cianetos/química , Complexo IV da Cadeia de Transporte de Elétrons/química , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Heme/antagonistas & inibidores , Heme/metabolismo , Hemeproteínas/química , Hemeproteínas/metabolismo , Hemoglobinas/química , Peroxidase do Rábano Silvestre/metabolismo , Hidróxidos/química , Cinética , Ligantes , Mitocôndrias/química , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , Oxirredução , Espécies Reativas de Oxigênio/metabolismo , Estirenos/química , Estirenos/farmacologia , Superóxidos/química , Termodinâmica
14.
Plant Biol (Stuttg) ; 22(3): 425-432, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32052535

RESUMO

Cyanide-resistant respiration in potato mitochondria is an important pathway for energy dissipation. It can be activated by high light; however, it is unclear what roles cyanide-resistant respiration plays in the response to high light stress in potato. We designed a CRISPR vector for the functional gene StAOX of the potato cyanide-resistant respiratory pathway. Agrobacterium tumefaciens GV3101 was transformed into potato. Hydrogen peroxide level, MDA content, antioxidant activity and cyanide-resistant respiratory capacity of potato leaves under high light stress were determined. Photosynthetic efficiency and chlorophyll content were determined. In addition, the operation of the malate-oxaloacetate shuttle route and transcription level of photorespiration-related enzymes were also examined. The results showed that two base substitutions occurred at the sequencing target site on leaves of the transformed potato. Accumulation of ROS and increased membrane lipid peroxidation were detected in the transformed potato leaves and lower photosynthetic efficiency was observed. The transcription level of the malate-oxaloacetate shuttle route and photorespiration-related enzymes also significantly increased. These results indicate that the cyanide-resistant respiration is an important physiological pathway in potato in response to high light stress. It also suggests that plant cyanide-resistant respiration is closely related to photosynthesis. This implies the unexplored importance of plant cyanide-resistant respiration in plant photosynthesis, energy conversion and carbon skeleton formation.


Assuntos
Respiração Celular , Cianetos , Resistência a Medicamentos , Luz , Folhas de Planta , Solanum tuberosum , Agrobacterium tumefaciens/genética , Respiração Celular/efeitos dos fármacos , Respiração Celular/efeitos da radiação , Clorofila , Cianetos/toxicidade , Oxirredutases/genética , Fotossíntese , Folhas de Planta/metabolismo , Folhas de Planta/efeitos da radiação , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Solanum tuberosum/efeitos da radiação
15.
J Neurosci ; 40(9): 1975-1986, 2020 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-32005765

RESUMO

Mitochondrial dysfunction is critically involved in Parkinson's disease, characterized by loss of dopaminergic neurons (DaNs) in the substantia nigra (SNc), whereas DaNs in the neighboring ventral tegmental area (VTA) are much less affected. In contrast to VTA, SNc DaNs engage calcium channels to generate action potentials, which lead to oxidant stress by yet unknown pathways. To determine the molecular mechanisms linking calcium load with selective cell death in the presence of mitochondrial deficiency, we analyzed the mitochondrial redox state and the mitochondrial membrane potential in mice of both sexes with genetically induced, severe mitochondrial dysfunction in DaNs (MitoPark mice), at the same time expressing a redox-sensitive GFP targeted to the mitochondrial matrix. Despite mitochondrial insufficiency in all DaNs, exclusively SNc neurons showed an oxidized redox-system, i.e., a low reduced/oxidized glutathione (GSH-GSSG) ratio. This was mimicked by cyanide, but not by rotenone or antimycin A, making the involvement of reactive oxygen species rather unlikely. Surprisingly, a high mitochondrial inner membrane potential was maintained in MitoPark SNc DaNs. Antagonizing calcium influx into the cell and into mitochondria, respectively, rescued the disturbed redox ratio and induced further hyperpolarization of the inner mitochondrial membrane. Our data therefore show that the constant calcium load in SNc DaNs is counterbalanced by a high mitochondrial inner membrane potential, even under conditions of severe mitochondrial dysfunction, but triggers a detrimental imbalance in the mitochondrial redox system, which will lead to neuron death. Our findings thus reveal a new mechanism, redox imbalance, which underlies the differential vulnerability of DaNs to mitochondrial defects.SIGNIFICANCE STATEMENT Parkinson's disease is characterized by the preferential degeneration of dopaminergic neurons (DaNs) of the substantia nigra pars compacta (SNc), resulting in the characteristic hypokinesia in patients. Ubiquitous pathological triggers cannot be responsible for the selective neuron loss. Here we show that mitochondrial impairment together with elevated calcium burden destabilize the mitochondrial antioxidant defense only in SNc DaNs, and thus promote the increased vulnerability of this neuron population.


Assuntos
Antioxidantes/metabolismo , Cálcio/toxicidade , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Doenças Mitocondriais/metabolismo , Doenças Mitocondriais/patologia , Substância Negra/metabolismo , Substância Negra/patologia , Animais , Calbindina 1/metabolismo , Morte Celular , Cianetos/toxicidade , Feminino , Masculino , Potencial da Membrana Mitocondrial , Camundongos , Membranas Mitocondriais/metabolismo , Oxirredução , Estresse Oxidativo , Área Tegmentar Ventral/metabolismo , Área Tegmentar Ventral/patologia
16.
Clin Toxicol (Phila) ; 58(1): 29-35, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31008657

RESUMO

Background: Cyanide is a metabolic poison used in multiple industries and is a high threat chemical agent. Current antidotes require intravenous administration, limiting their usefulness in a mass casualty scenario. Sodium tetrathionate reacts directly with cyanide yielding thiosulfate and the non-toxic compound thiocyanate. Thiosulfate, in turn, neutralizes a second molecule of cyanide, thus, per mole, sodium tetrathionate neutralizes two moles of cyanide. Historical studies examined its efficacy as a cyanide antidote, but it has not been evaluated in a clinically relevant, large animal model, nor has it previously been administered by intramuscular injection.Objective: The objective of this study is to evaluate the efficacy of intramuscular sodium tetrathionate on survival and clinical outcomes in a large, swine model of severe cyanide toxicity.Methods: Anesthetized swine were instrumented for continuous monitoring of hemodynamics, then acclimated and breathing spontaneously prior to potassium cyanide infusion (0.17 mg/kg/min). At 6-min post-apnea (no breaths for 20 s), the cyanide infusion was terminated, and animals were treated with sodium tetrathionate (∼18 mg/kg) or normal saline control. Clinical parameters and laboratory values were evaluated at various time points until death or termination of the experiment (90 min post-treatment).Results: Laboratory values, vital signs, and time to apnea were similar in both groups at baseline and treatment. Survival in the sodium tetrathionate treated group was 100% and 17% in controls (p = 0.0043). All animals treated with sodium tetrathionate returned to breathing at a mean time of 10.85 min after antidote, and all but one control remained apneic through end of the experiment. Animals treated with tetrathionate showed improvement in blood lactate (p ≤ 0.002) starting at 30 min post-treatment. The average time to death in the control group is 63.3 ± 23.2 min. No systemic or localized adverse effects of intramuscular administration of sodium tetrathionate were observed.Conclusion: Sodium tetrathionate significantly improves survival and clinical outcomes in a large, swine model of acute cyanide poisoning.


Assuntos
Antídotos/uso terapêutico , Cianetos/toxicidade , Ácido Tetratiônico/uso terapêutico , Animais , Antídotos/administração & dosagem , Cianetos/antagonistas & inibidores , Modelos Animais de Doenças , Feminino , Injeções Intramusculares , Suínos , Ácido Tetratiônico/administração & dosagem
17.
Molecules ; 24(15)2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31370148

RESUMO

A novel functional ion-exchange/adsorption metal organic resin (MOR), TEBAC-HKUST-1, was prepared and characterized. Ethanedithiol was used as the grafting agent to introduce thiol groups onto HKUST-1, and 4-vinylbenzyl chloride was then grafted onto SH-HKUST-1 using thiol groups. Finally, the quaternary ammonium functional group was immobilized onto the carrier by performing a quaternization reaction. The structure and property of TEBAC-HKUST-1 MOR were characterized by TGA, N2 adsorption-desorption, FTIR, SEM, and XRD. TEBAC-HKUST-1 MOR was used to remove metal cyanide complexes from wastewater. The adsorption was rapid, and the metal cyanide complexes including Pt(CN)42-, Co(CN)63-, Cu(CN)32-, and Fe(CN)63- were removed in 30 min. TEBAC-HKUST-1 MOR exhibited a high stability in neutral and weak basic aqueous solutions. Furthermore, Pt(II) could be efficiently recovered through two-step elution. The recovery rate of Pt(II) for five cycles were over 92.0% in the mixture solution containing Pt(CN)42-, Co(CN)63-, Cu(CN)32-, and Fe(CN)63-. The kinetic data were best fitted with the pseudo second-order model. Moreover, the isothermal data were best fitted with the Langmuir model. The thermodynamic results show that the adsorption is a spontaneous and exothermic process. TEBAC-HKUST-1 MOR not only exhibited excellent ability for the rapid removal of metal cyanide complexes, but also provided a new idea for the extraction of noble metals from cyanide-contaminated water.


Assuntos
Cianetos/isolamento & purificação , Compostos Organometálicos/química , Águas Residuárias/química , Purificação da Água/métodos , Adsorção , Complexos de Coordenação/química , Cianetos/química , Cianetos/toxicidade , Humanos , Concentração de Íons de Hidrogênio , Resinas de Troca Iônica/química , Cinética , Paládio/química , Termodinâmica , Poluentes Químicos da Água
18.
Chemistry ; 25(62): 14214-14222, 2019 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-31452291

RESUMO

A series of new ruthenium(II) vinyl complexes has been prepared incorporating perylenemonoimide (PMI) units. This fluorogenic moiety was functionalised with terminal alkyne or pyridyl groups, allowing attachment to the metal either as a vinyl ligand or through the pyridyl nitrogen. The inherent low solubility of the perylene compounds was improved through the design of poly-PEGylated (PEG=polyethylene glycol) units bearing a terminal alkyne or a pyridyl group. By absorbing the compounds on silica, vapours and gases could be detected in the solid state. The reaction of the complexes [Ru(CH=CH-PerIm )Cl(CO)(py-3PEG)(PPh3 )2 ] and [Ru(CH=CH-3PEG)Cl(CO)(py-PerIm )(PPh3 )2 ] with carbon monoxide, isonitrile or cyanide was found to result in modulation of the fluorescence behaviour. The complexes were observed to display solvatochromic effects and the interaction of the complexes with a wide range of other species was also studied. The study suggests that such complexes have potential for the detection of gases or vapours that are toxic to humans.


Assuntos
Monóxido de Carbono/análise , Cianetos/análise , Corantes Fluorescentes/química , Imidas/química , Nitrilas/análise , Perileno/análogos & derivados , Rutênio/química , Alcinos/química , Monóxido de Carbono/toxicidade , Complexos de Coordenação/química , Cianetos/toxicidade , Nitrilas/toxicidade , Perileno/química , Piridinas/química
19.
J Food Sci ; 84(7): 1986-1991, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31192461

RESUMO

Cassava leaves are a valuable source of protein but the cyanogenic potential limits their use as food and feed. Four different treatments were investigated to detoxify cassava leaves. Thermal (55 °C for 6 hr), sodium bicarbonate (0.4% NaHCO3 , 55 °C for 6 hr), enzymatic (0.32% Multifect® GC Extra, 4 hr), and ultrasonic treatments (500 W, 35 kHz, 55 °C, 0.25 hr) reduced the total cyanide (µg HCN equivalents per g fresh leaf or ppm) content by 90%, 93%, 82%, and 84% while the cyanide content reduction in the respective controls was 85%, 90%, 79%, and 84%, respectively. The sodium bicarbonate treatment was found to be the most effective treatment. Therefore, it was further optimized by varying time and temperature. A significant effect on the cyanide content was observed by changing the incubation time while no significant effect of temperature was noticed. Nevertheless, extended incubation time during sodium bicarbonate treatment reduced ascorbic acid content by 7% and 39% when leaves were incubated with sodium bicarbonate for 0.5 hr and 48 hr, respectively. PRACTICAL APPLICATION: Cyanogenic glucosides are the major toxic compound in cassava leaves, which limits their use as food and feed. The methods proposed in this study can be used to detoxify cassava leaves, which are generally considered as an inferior by-product. Hence, detoxified cassava leaves may contribute to fulfil world protein demand in an eco-sustainable way.


Assuntos
Cianetos/química , Manipulação de Alimentos/métodos , Glicosídeos/química , Manihot/química , Folhas de Planta/química , Biocatálise , Cianetos/toxicidade , Enzimas/química , Glicosídeos/toxicidade , Temperatura Alta , Manihot/toxicidade , Folhas de Planta/toxicidade , Bicarbonato de Sódio/química , Ultrassom
20.
World J Microbiol Biotechnol ; 35(5): 70, 2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31011828

RESUMO

Cyanide is a nitrile which is used extensively in many industries like jewelry, mining, electroplating, plastics, dyes, paints, pharmaceuticals, food processing, and coal coking. Cyanides pose a serious health hazard due to their high affinity towards metals and cause malfunction of cellular respiration by inhibition of cytochrome c oxidase. This inhibition ultimately leads to histotoxic hypoxia, increased acidosis, reduced the functioning of the central nervous system and myocardial activity. Different physicochemical processes including oxidation by hydrogen peroxide, alkaline chlorination, and ozonization have been used to reduce cyanide waste from the environment. Microbial cyanide degradation which is considered as one the most successful techniques is used to take place through different biochemical/metabolic pathways involving reductive, oxidative, hydrolytic or substitution/transfer reactions. Groups of enzymes involved in microbial degradation are cyanidase, cyanide hydratase, formamidase, nitrilase, nitrile hydratase, cyanide dioxygenase, cyanide monooxygenase, cyanase and nitrogenase. In the future, more advancement of omics technologies and protein engineering will help us to recoup the environment from cyanide effluent. In this review, we have discussed the origin and environmental distribution of cyanide waste along with different bioremediation pathways and enzymes involved therein.


Assuntos
Bactérias/enzimologia , Cianetos/metabolismo , Fungos/enzimologia , Resíduos Industriais/análise , Plantas/enzimologia , Amidoidrolases , Aminoidrolases , Bactérias/classificação , Bactérias/metabolismo , Biodegradação Ambiental , Carbono-Nitrogênio Liases , Cianetos/toxicidade , Fungos/metabolismo , Hidroliases , Hidrolases , Microbiologia Industrial , Nitrogenase , Oxirredução , Plantas/classificação , Plantas/metabolismo , Sulfurtransferases , Tiossulfato Sulfurtransferase
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