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Journal of Medical Toxicology :... Jul 2021Cyanide is a deadly poison, particularly with oral exposure where larger doses can occur before symptoms develop. Prior studies and multiple governmentagencies highlight...
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.
Topics: Administration, Oral; Animals; Antidotes; Cyanides; Humans; Models, Animal; Swine; Thiosulfates; Treatment Outcome
PubMed: 33821433
DOI: 10.1007/s13181-021-00836-5 -
British Journal of Anaesthesia Dec 1977The influence of sodium nitroprusside (SNP) on mitochondrial respiration was examined in rat liver mitochondria. The addition of SNP 1 mmol litre-1 during state 3...
The influence of sodium nitroprusside (SNP) on mitochondrial respiration was examined in rat liver mitochondria. The addition of SNP 1 mmol litre-1 during state 3 respiration inhibited the oxygen uptake by 63.4%. A mixture of SNP 1 mmol litre-1 and glutathione (GSH) 1 mmol litre-1 inhibited the oxygen uptake more markedly (by 75.9%). The cyanide concentrations were 0.01 mmol litre-1 with SNP alone and 0.15 mmol litre-1 with the mixture of SNP and GSH. Cyanide production from SNP in the presence of various reducing agents was studied in potassium phosphate 0.1 mol litre-1 buffer solution (pH 7.4) incubated at 37 degrees C. Cyanide was liberated markedly from SNP in the presence of GSH or ascorbate. Less cyanide was produced in the presence of NADH or NADPH. The rate of production of cyanide was dependent entirely upon the concentration of each reducing agent added. No cyanide was liberated when sodium dithionite or the oxidized forms of GSH, NAD or NADP were used. It was concluded that SNP is degradated to cyanide by a hydrogen donor and that the cyanide liberated in this manner inhibits the cytochrome oxidase activity of mitochondria in vivo.
Topics: Animals; Cyanides; Ferricyanides; In Vitro Techniques; Male; Mitochondria, Liver; Nitroprusside; Oxygen Consumption; Rats
PubMed: 588400
DOI: 10.1093/bja/49.12.1239 -
Biotechnology Reports (Amsterdam,... Dec 2020The molecular screening for laccase specific gene sequences in WRF03 (WRF03) using designed oligonucleotide primers analogous to the conserved sequences on the...
The molecular screening for laccase specific gene sequences in WRF03 (WRF03) using designed oligonucleotide primers analogous to the conserved sequences on the copper-binding regions of known laccases showed positive amplification with an amplicon size corresponding to 1500 bp. The purified WRF03 laccase (L) is a monomer with a molecular weight corresponding to 66 kDa. The enzyme had an optimal pH of 4.5 and temperature of 55 °C. L was most stable within pH of 5.5-6.5 and at a temperature range of 40-50 °C. Sodium azide, sodium cyanide and Fe greatly inhibited the enzyme activity. L showed more than 50 % decolourisation efficiency on coomassie brilliant blue (72.35 %) and malachite green (57.84 %) but displayed low decolourisation efficiency towards Azure B (1.78 %) and methylene blue (0.38 %). The results showed that WRF03 produces high-yield of true laccase with robust properties for biotechnological applications.
PubMed: 33299811
DOI: 10.1016/j.btre.2020.e00566 -
The Biochemical Journal Oct 19761. Treatment of liver microsomal fraction with 0.03-0.12% sodium deoxycholate and 0.005-0.06 mM carbonyl cyanide m-chlorophenylhydrazone decreases phospholipid-dependent...
1. Treatment of liver microsomal fraction with 0.03-0.12% sodium deoxycholate and 0.005-0.06 mM carbonyl cyanide m-chlorophenylhydrazone decreases phospholipid-dependent hydrophobicity of the microsomal membrane, assayed by the kinetics of 8-anilinonaphthalene-1-sulphonate binding and ethyl isocyanide difference spectra. 2. Sodium deoxycholate at a concentration of 0.01% lacks its detergent properties, but competitively inhibits aminopyrine binding and activates the initial rate of NADPH-cytochrome P-450 reductase. In the presence of 0.03-0.09% sodium deoxycholate the rate-limiting factor in p-hydroxylation of aniline is the content of cytochrome P-450. and that for N-demethylation of aminopyrine is the activity of NADPH-cytochrome P-450 reductase. 3. Carbonyl cyanide m-chlorophenylhydrazone has no effect on the binding and metabolism of aniline; investigation of its inhibiting effect on aminopyrine N-demethylase established that the rate-limiting reaction is the dissociation of the enzyme-substrate complex in the microsomal preparations. 4. In the mechanism of action of carbonyl cyanide m-chlorophenylhydrazone the key step may be the electrostatic interaction of its protonated form and one of the forms of activated oxygen at the catalytic centre of cytochrome P-450. 5. at least two different phospholipid-dependent hydrophobic zones are assumed to exist in the microsomal membrane, both coupled with cytochrome P-450. One of them reveals selective sensitivity to the protonation action of carbonyl cyanide m-chlorophenylhydrazone and contains the 'binding protein' for type I substrates and NADPH-cytochrome P-450 reductase; the other contains the cytochrome P-450 haem group and binding sites for type II substrates.
Topics: Aminopyrine; Aminopyrine N-Demethylase; Aniline Compounds; Anilino Naphthalenesulfonates; Animals; Carbonyl Cyanide m-Chlorophenyl Hydrazone; Cyanides; Cytochrome P-450 Enzyme Inhibitors; Cytochrome Reductases; Deoxycholic Acid; Hemeproteins; Hydrogen-Ion Concentration; Kinetics; Male; Microsomes, Liver; NADPH-Ferrihemoprotein Reductase; Nitriles; Protein Binding; Rats
PubMed: 12746
DOI: 10.1042/bj1600075 -
British Journal of Anaesthesia May 1987Plasma and red cell cyanide, and plasma thiocyanate, concentrations were measured in 30 patients undergoing elective nitroprusside-induced hypotension. One randomly... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Plasma and red cell cyanide, and plasma thiocyanate, concentrations were measured in 30 patients undergoing elective nitroprusside-induced hypotension. One randomly selected group (n = 15), who received 0.21-0.70 mg kg-1 over periods of 50-160 min, were given a bolus of sodium thiosulphate 10.6-38.5 mg kg-1 immediately on cessation of the nitroprusside administration. The other group, who received infusions of 0.11-0.85 mg kg-1 for periods of 59-197 min, received no antidote. Cyanide concentrations, expressed as a percentage of the immediate post-infusion values, were significantly lower in the treated group in all subsequent blood samples (at 10, 30 and 60 min; plasma cyanide P less than 0.05; red cell cyanide P less than 0.001). Improved cyanide metabolism was further demonstrated by a sharp increase in mean plasma thiocyanate concentration (P less than 0.05) in the group receiving the antidote.
Topics: Adult; Antidotes; Cyanides; Erythrocytes; Female; Ferricyanides; Humans; Hypotension, Controlled; Male; Nitroprusside; Thiocyanates; Thiosulfates
PubMed: 3580232
DOI: 10.1093/bja/59.5.531 -
International Journal of Molecular... Jun 2023In this paper, three imidazolium-based ionic liquids, viz., 1-butyl-3-undecyl imidazolium bromide ([BUIm]Br), 1-butyl-3-octyl imidazolium bromide ([BOIm]Br), and...
In this paper, three imidazolium-based ionic liquids, viz., 1-butyl-3-undecyl imidazolium bromide ([BUIm]Br), 1-butyl-3-octyl imidazolium bromide ([BOIm]Br), and 1-butyl-3-hexadecyl imidazolium bromide ([BCIm]Br), were synthesized. Three novel microemulsions systems were constructed and then were used to recover Pd (II) from cyanide media. Key extraction parameters such as the concentration of ionic liquids (ILs), equilibration time, phase ratio (R), and pH were evaluated. The [BUIm]Br/n-heptane/n-pentanol/sodium chloride microemulsion system exhibited a higher extraction percentage of Pd (II) than the [BOIm]Br/n-heptane/n-pentanol/sodium chloride and [BCIm]Br/n-heptane/n-pentanol/sodium chloride microemulsion systems. Under the optimal conditions (equilibrium time of 10 min and pH 10), the extraction percentages of these metals were all higher than 98.5% when using the [BUIm]Br/n-heptane/n-pentanol/sodium chloride microemulsion system. Pd(CN) was separated through a two-step stripping procedure, in which Fe (III) and Co (III) were first separated using KCl solution, then Pd(CN) was stripped using KSCN solution (separation factors of Pd from Fe and Co exceeded 10). After five extraction-recovery experiments, the recovery of Pd (II) through the microemulsion system remained over 90%. The Pd (II) extraction mechanism of the ionic liquid [BUIm]Br was determined to occur via anion exchange, as shown by spectral analysis (UV, FTIR), Job's method, and DFT calculations. The proposed process has potential applications for the comprehensive treatment of cyanide metallurgical wastewater.
Topics: Cyanides; Ionic Liquids; Palladium; Bromides; Sodium Chloride
PubMed: 37445887
DOI: 10.3390/ijms241310709 -
International Journal of Molecular... Dec 2022Ischaemia, followed by reperfusion, causes the generation of reactive oxygen species, overproduction of peroxynitrite, activation of matrix metalloproteinases (MMPs),...
Ischaemia, followed by reperfusion, causes the generation of reactive oxygen species, overproduction of peroxynitrite, activation of matrix metalloproteinases (MMPs), and subsequently the degradation of heart contractile proteins in the cardiomyocytes. Klotho is a membrane-bound or soluble protein that regulates mineral metabolism and has antioxidative activity. This study aimed to examine the influence of Klotho protein on the MMP-mediated degradation of contractile proteins during ischaemia/reperfusion injury (IRI) to the cardiomyocytes. Human cardiac myocytes (HCM) underwent in vitro chemical IRI (with sodium cyanide and deoxyglucose), with or without the administration of recombinant Klotho protein. The expression of MMP genes, the expression and activity of MMP proteins, as well as the level of contractile proteins such as myosin light chain 1 (MLC1) and troponin I (TnI) in HCM were measured. Administration of Klotho protein resulted in a decreased activity of MMP-2 and reduced the release of MLC1 and TnI that followed in cells subjected to IRI. Thus, Klotho protein contributes to the inhibition of MMP-dependent degradation of contractile proteins and prevents injury to the cardiomyocytes during IRI.
Topics: Humans; Contractile Proteins; Klotho Proteins; Myocardial Reperfusion Injury; Myocytes, Cardiac; Troponin I; Reperfusion Injury
PubMed: 36555091
DOI: 10.3390/ijms232415450 -
Biochimica Et Biophysica Acta Feb 2012It has been known that the inhibition of mitochondrial cytochrome c oxidase is one of the earliest events occurring under hypoxia and this inhibition can lead to...
It has been known that the inhibition of mitochondrial cytochrome c oxidase is one of the earliest events occurring under hypoxia and this inhibition can lead to neuronal damages. Thus, the cytochrome c oxidase inhibitor sodium cyanide (NaCN) is widely used to produce a model of chemical hypoxia by inhibiting this enzyme. However, the downstream signaling pathways of the inhibition of the cytochrome c oxidase remain to be studied. In the present paper, we used sodium cyanide to mimic the inhibition of the mitochondrial cytochrome c oxidase and studied its effect on glutamate release in synaptosomes from the prefrontal cortex using on-line fluorimetry. We also further investigated the mechanisms underlying the enhancing effect of sodium cyanide on glutamate release using pharmacological approaches combined with other techniques. The results showed that sodium cyanide significantly increased glutamate release from synaptosomes of prefrontal cortex; the broad-spectrum free radical scavenger MnTBAP and melatonin completely abolished the effect of sodium cyanide on glutamate release; the H2O2-NMDA receptor pathway mediated one part, whereas the lipid peroxyl radicals-ATP synthase pathway mediated another part of the sodium cyanide-induced glutamate release; scavenging H2O2 and enhancing ATP synthase activity could completely abolish the sodium cyanide-induced glutamate release.
Topics: Adenosine Triphosphate; Animals; Calcium Channels; Cyclic AMP-Dependent Protein Kinases; Enzyme Inhibitors; Free Radicals; Glutamic Acid; Hydrogen Peroxide; Hypoxia; Lipid Peroxidation; Male; Mitochondrial Proton-Translocating ATPases; Oxidants; Prefrontal Cortex; Protein Kinase C; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate; Signal Transduction; Sodium Cyanide; Synaptosomes; Valine
PubMed: 22057390
DOI: 10.1016/j.bbamcr.2011.10.004 -
Cardiology Journal 2022Acute heart ischemia followed by reperfusion leads to overproduction of reactive oxygen/ /nitrogen species (ROS/RNS), disrupted expression of nitric oxide synthase (NOS)...
BACKGROUND
Acute heart ischemia followed by reperfusion leads to overproduction of reactive oxygen/ /nitrogen species (ROS/RNS), disrupted expression of nitric oxide synthase (NOS) and unbalanced glucose metabolism. Klotho is a membrane-bound or soluble protein that exerts protective activity in many organs. While Klotho is produced mainly in the kidneys and brain, it has been recently proven that Klotho is expressed in the cardiomyocytes as well. This study aimed to show the influence of the Klotho protein on oxidative/nitrosative stress and metabolic function of the cardiomyocytes subjected to ischemia/reperfusion (I/R) injury.
METHODS
Human cardiac myocytes underwent in vitro chemical I/R (with sodium cyanide and 2-deoxyglucose), in the presence or absence of the recombinant human Klotho protein. The present study included an investigation of cell injury markers, level of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX), level of oxidative/nitrosative stress and metabolic processes of the cardiomyocytes.
RESULTS
Administration of Klotho protein resulted in mitigation of injury, decreased level of NOX2 and NOX4, reduced generation of ROS/RNS and hydrogen peroxide (H2O2), decreased expression of inducible NOS and limited production of nitrates/nitrites in cells under I/R. Glucose uptake and lactate production in the cardiomyocytes subjected to I/R were normalized after Klotho supplementation.
CONCLUSIONS
The Klotho protein participates in the regulation of redox balance and supports metabolic homeostasis of the cardiomyocytes and hence, contributes to protection against I/R injury.
Topics: Deoxyglucose; Glucose; Humans; Hydrogen Peroxide; Ischemia; Lactates; Myocytes, Cardiac; NADP; NADPH Oxidases; Nitrates; Nitric Oxide Synthase; Nitrites; Nitrogen; Oxidation-Reduction; Oxidative Stress; Oxygen; Reactive Nitrogen Species; Reactive Oxygen Species; Reperfusion Injury; Sodium Cyanide
PubMed: 34967938
DOI: 10.5603/CJ.a2021.0174 -
Korean Journal of Anesthesiology Apr 2016Sodium nitroprusside (SNP) is an anti-hypertensive drug, commonly used to decrease the systemic vascular resistance and lower the blood pressure. When the amount of...
Sodium nitroprusside (SNP) is an anti-hypertensive drug, commonly used to decrease the systemic vascular resistance and lower the blood pressure. When the amount of cyanide generated by the SNP exceeds the metabolic capacity for detoxification, cyanide toxicity occurs. Under general anesthesia and cardiopulmonary bypass (CPB), it may be difficult to detect the development of cyanide toxicity. In cardiac surgical patients, hemolysis, hypothermia and decreased organ perfusion, which emphasize the risk of cyanide toxicity, may develop as a consequence of CPB. In particular, hemolysis during CPB may cause an unexpected overproduction of cyanide due to free hemoglobin release. We experienced a patient who demonstrated SNP tachyphylaxis and cyanide toxicity during CPB, even though the total amount of SNP administered was much lower than the recommended dose. We therefore report this case with a review of the relevant literature.
PubMed: 27064896
DOI: 10.4097/kjae.2016.69.2.181