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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 -
Environmental Science and Pollution... Jan 2024For over two hundred years, cyanide has served as the primary reagent for gold extraction. However, due to its high toxicity, the use of cyanide poses significant risks....
For over two hundred years, cyanide has served as the primary reagent for gold extraction. However, due to its high toxicity, the use of cyanide poses significant risks. Traditional low-toxicity leaching reagents have limitations that restrict their widespread industrial application, leading to the necessity for the development of new, efficient, and low-toxic gold leaching reagents to support sustainable gold production. In this study, a novel, efficient, and low-toxicity gold extraction reagent was synthesized at high temperatures by combining urea, sodium carbonate, and a specific iron salt. The research delved into the leaching ability of the reagent under different synthesis conditions and examined the generation of free cyanide content as a by-product. Findings indicated that reagents synthesized with either potassium ferrocyanide or potassium ferricyanide displayed comparable leaching capabilities. Reagents synthesized at 800 °C exhibited lower levels of free cyanide ions and reduced toxicity. Additionally, this reagent demonstrated exceptional selectivity for gold, while in minimal dissolution of copper, iron, nickel, lead, and iron from computer central processing unit (CPU) pins. Under optimal conditions, the efficiency of gold extraction from CPU pins reached 94.65%. Hence, this reagent holds significant potential for the low-toxicity extraction of gold from electronic waste or auriferous concentrates.
Topics: Indicators and Reagents; Temperature; Gold; Electronic Waste; Cyanides; Iron; Copper
PubMed: 38157179
DOI: 10.1007/s11356-023-31259-0 -
Clinical and Experimental Pharmacology... Dec 2021Serotonin (5-HT) accumulates in the heart during myocardial ischaemia and induces deleterious effects on the cardiomyocytes. We aimed to investigate whether...
Serotonin (5-HT) accumulates in the heart during myocardial ischaemia and induces deleterious effects on the cardiomyocytes. We aimed to investigate whether carrier-mediated 5-HT efflux contributed to the increase in interstitial 5-HT level during ischaemia. Using microdialysis technique applied to the heart of anaesthetised Wistar rats, myocardial interstitial concentration of 5-HT was measured by electro-chemical detection coupled with high-performance liquid chromatography (HPLC-ECD) while simultaneously various pharmacological agents, which create a similar condition to ischaemia, were locally administered by reverse-microdialysis. Sodium cyanide-induced chemical anoxia increased dialysate 5-HT concentration. A similar increase in dialysate 5-HT concentration was induced by ouabain, an inhibitor of sodium-potassium ATPase and reserpine, an inhibitor of vesicular monoamine transporter. Fluoxetine, a selective serotonin reuptake inhibitor raised the baseline level of 5-HT, and neither sodium cyanide nor the combination of ouabain and reserpine induced further increase in 5-HT in the presence of fluoxetine. The results indicate that reverse transport of 5-HT via SERT, which is caused by an impaired ion gradient, contributes to the rise in interstitial level of 5-HT during ischaemia suggesting carrier-mediated 5-HT efflux occurs in the heart in vivo.
Topics: Serotonin
PubMed: 34411314
DOI: 10.1111/1440-1681.13576 -
Journal of Chromatography. B,... Apr 2018Itraconazole (ITZ) is a first-generation triazole-containing antifungal agent that effectively treats various fungal infections. As ITZ has a better safety profile than...
Itraconazole (ITZ) is a first-generation triazole-containing antifungal agent that effectively treats various fungal infections. As ITZ has a better safety profile than that of ketoconazole (KCZ), ITZ has been used worldwide for over 25 years. However, few reports have explored the metabolic profile of ITZ, and the underlying mechanism of ITZ-induced liver injury is not clearly understood. In the present study, we revisited ITZ metabolism in humans, using a non-targeted metabolomics approach, and identified several novel metabolic pathways including O-dearylation, piperazine oxidation, and piperazine-N,N'-deethylation. Furthermore, we explored the formation of reactive ITZ metabolites using trapping agents as surrogates, to assess the possibility of metabolism-mediated toxicity. We found that ITZ and its metabolites did not form any adducts with nucleophiles including glutathione, potassium cyanide, and semicarbazide. The present study expands our knowledge of ITZ metabolism and supports the suggestion that ITZ has a better safety profile than that of KCZ in terms of metabolism-mediated toxicity.
Topics: Chromatography, Liquid; Humans; Itraconazole; Mass Spectrometry; Metabolome; Metabolomics; Microsomes, Liver
PubMed: 29524695
DOI: 10.1016/j.jchromb.2018.02.041 -
Inorganic Chemistry Dec 2020Water-soluble complexes are desirable for the aqueous detoxification of cyanide. Molybdenum complexes with α-amino acid and disulfide ligands with the formula...
Water-Soluble α-Amino Acid Complexes of Molybdenum as Potential Antidotes for Cyanide Poisoning: Synthesis and Catalytic Studies of Threonine, Methionine, Serine, and Leucine Complexes.
Water-soluble complexes are desirable for the aqueous detoxification of cyanide. Molybdenum complexes with α-amino acid and disulfide ligands with the formula K[(L)MoO(μ-S)(S)] (L = leu (), met (), thr (), and ser ()) were synthesized in a reaction of [(DMF)MoO(μ-S)(S)] with deprotonated α-amino acids; leu, met, thr, and ser are the carboxylate anions of l-leucine, l-methionine, l-threonine, and l-serine, respectively. Potassium salts of α-amino acids (leu (), met (), thr (), and ser ()) were prepared as precursors for complexes -, respectively, by employing a nonaqueous synthesis route. The ligand exchange reaction of [MoO(μ-S)(DMF)](I) with deprotonated α-amino acids afforded -α-amino acid complexes, [(L)MoO(μ-S)] (-). A -α-amino acid complex, [(leu)MoO(μ-S)(μ-leu + H)] (; leu + H is the carboxylate anion of l-leucine with the amine protonated), formed in the reaction with leucine. crystallized from methanol with a third weakly bonded leucine as a bridging bidentate carboxylate. An adduct of with SCN coordinated, , crystallized and was structurally characterized. Complexes - are air stable and highly water-soluble chiral molecules. Cytotoxicity studies in the A549 cell line gave IC values that range from 80 to 400 μM. Cyclic voltammetry traces of - show solvent-dependent irreversible electrochemical behavior. Complexes - demonstrated the ability to catalyze the reaction of thiosulfate and cyanide to exhaustively transform cyanide to thiocyanate in less than 1 h.
Topics: A549 Cells; Amino Acids; Antidotes; Cell Survival; Cyanides; Humans; Inhibitory Concentration 50; Leucine; Magnetic Resonance Spectroscopy; Mass Spectrometry; Methionine; Models, Molecular; Molecular Structure; Molybdenum; Serine; Solubility; Spectrophotometry, Infrared; Thiocyanates; Threonine; Water
PubMed: 33249838
DOI: 10.1021/acs.inorgchem.0c02672 -
Interdisciplinary Toxicology Sep 2017Cyanogens are widely used in industries and their toxicity is mainly due to cyanogenesis. The antidotes for cyanide are usually instituted for the management of cyanogen...
Protective efficacy of various carbonyl compounds and their metabolites, and nutrients against acute toxicity of some cyanogens in rats: biochemical and physiological studies.
Cyanogens are widely used in industries and their toxicity is mainly due to cyanogenesis. The antidotes for cyanide are usually instituted for the management of cyanogen poisoning. The present study reports the protective efficacy of 14 carbonyl compounds and their metabolites, and nutrients (1.0 g/kg; oral; +5 min) against acute oral toxicity of acetonitrile (ATCN), acrylonitrile (ACN), malononitrile (MCN), propionitrile (PCN), sodium nitroprusside (SNP), succinonitrile (SCN), and potassium ferricyanide (PFCN) in rats. Maximum protection index was observed for alpha-ketoglutarate (A-KG) against MCN and PCN (5.60), followed by dihydroxyacetone (DHA) against MCN (2.79). Further, MCN (0.75 LD50) caused significant increase in cyanide concentration in brain, liver and kidney and inhibition of cytochrome c oxidase activity in brain and liver, which favorably responded to A-KG and DHA treatment. Up-regulation of inducible nitric oxide synthase by MCN, PCN and SNP, and uncoupling protein by PCN and SNP observed in the brain was abolished by A-KG administration. However, no DNA damage was detected in the brain. MCN and SNP significantly decreased the mean arterial pressure, heart rate, respiratory rate and neuromuscular transmission, which were resolved by A-KG. The study suggests a beneficial effect of A-KG in the treatment of acute cyanogen poisoning.
PubMed: 30123030
DOI: 10.1515/intox-2017-0001 -
Comparative Medicine Oct 2018Cyanide is a readily available and potentially lethal substance. Oral exposure can result in larger doses, compared with other routes. Currently, there are no antidotes...
Cyanide is a readily available and potentially lethal substance. Oral exposure can result in larger doses, compared with other routes. Currently, there are no antidotes specific for use in the treatment of oral cyanide poisoning, and studies cannot be done in humans. We report on a new large animal model of oral cyanide toxicity to evaluate potential antidotes. Six female swine (; weight, 45 to 55 kg) were anesthetized, intubated, and instrumented. Animals received a KCN bolus of either 5 or 8 mg/kg delivered via orogastric tube. Time to apnea was recorded; parameters monitored included heart rate, respiratory rate, blood pressure, pulse oximetry, end-tidal CO2, arterial blood gasses, and lactate concentrations. The Welch test was used to calculate confidence intervals, mean, and standard deviation, and a Kaplan-Meier survival curve was used to compare survival between the 2 groups. At baseline, all animals in both groups were similar. Animals in the 5-mg/kg group had a more rapid time to apnea (5.1 ± 2.1 min), longer time to death (48.5 ± 38.1 min), and a greater rate of survival than the 8-mg/kg group (apnea, 10.6 ± 10.7 min; death, 26.1 ± 5.8 min). All animals displayed signs of toxicity (acidemia, hyperlactatemia, hypotension, apnea). We here report a large animal (swine) model of oral cyanide poisoning with dose-dependent effects in regard to time to death and survival rate. This model likely will be valuable for the development of medical countermeasures for oral cyanide poisoning.
Topics: Administration, Oral; Animals; Disease Models, Animal; Female; Kaplan-Meier Estimate; Monitoring, Physiologic; Potassium Cyanide; Swine
PubMed: 30208987
DOI: 10.30802/AALAS-CM-18-000041 -
Journal of Analytical Toxicology Jul 2018A man was found dead in a hotel located near Rome (Italy). The man was still holding a syringe attached to a butterfly needle inserted in his left forearm vein. The...
A man was found dead in a hotel located near Rome (Italy). The man was still holding a syringe attached to a butterfly needle inserted in his left forearm vein. The syringe contained a cloudy pinkish fluid. In the hotel room the Police found a broken propofol glass vial plus four sealed ones, an opened NaCl plastic vial and six more still sealed, and a number of packed smaller disposable syringes and needles. An opened plastic bottle containing a white crystalline powder labeled as potassium cyanide was also found. Systematic toxicological analysis (STA), carried out on blood, urine and bile, evidenced only the presence of propofol in blood and bile. So the validated L-L extraction protocol and the GC/MS-TOF method for the confirmation of propofol in the biological fluids optimized in our laboratory was applied to blood, urine and bile. The concentration of propofol resulted to be 0.432 μg/mL in blood and 0.786 μg/mL in bile. The quantitative determination of cyanide in blood was carried out by microdiffusion technique coupled to spectrophotometric detection obtaining a cyanide concentration of 5.3 μg/mL. The quantitative determination was then confirmed by GC/NPD and the concentration of cyanide resulted to be 5.5 μg/mL in blood and 1.7 μg/mL in bile. Data emerging from autopsy findings, histopathological exams and the concentrations of cyanide suggested that death might be due to poisoning caused by cyanide, however, respiratory depression caused by propofol could not be excluded.
Topics: Adult; Autopsy; Bile; Cause of Death; Chromatography, Gas; Drug Overdose; Fatal Outcome; Forensic Toxicology; Gas Chromatography-Mass Spectrometry; Humans; Male; Potassium Cyanide; Predictive Value of Tests; Propofol; Spectrophotometry, Ultraviolet; Substance Abuse Detection
PubMed: 30007331
DOI: 10.1093/jat/bky015 -
Environmental Monitoring and Assessment Jul 2018The present study describes the use of poison baits against so-called pest species in Greece and explores various aspects of this illegal practice. Data were collected...
The present study describes the use of poison baits against so-called pest species in Greece and explores various aspects of this illegal practice. Data were collected from 2000 to 2016, and a total of 1015 poisoning incidents in rural areas causing the death of 3248 animals were examined. In 58.7% of investigated cases, the motives remained unknown; in the remaining cases, human-wildlife conflicts and retaliatory actions among stakeholders (e.g., hunters vs. livestock breeders) were found to be the main reasons for poison bait use. The target animals for these actions were mainly mammalian carnivores, and stray canids, all of which were blamed for livestock and game losses. Avian scavengers were the wildlife species most affected by secondary poisoning (30% of the wildlife fatalities), whereas shepherd dogs accounted for 66.4% of domestic animal losses. Toxicological analyses showed that a wide range of chemical substances were used, mostly legal or banned pesticides (e.g., carbamates, organophosphates, and organochlorines) and potassium cyanide. Furthermore, the widespread trafficking of black marketed insecticides was also recorded, with methomyl (in powder form) and carbofuran being most common. The majority of poisoning events (72%) took place outside protected areas, while in approximately 73.4% of them, no official reporting to the competent authorities was made. Overall, the study highlights the significant impact of illegal poison bait use on wildlife in Greece and addresses its extreme socioeconomic complexity. The need for an integrated national anti-poison strategy is discussed.
Topics: Animals; Animals, Wild; Carbofuran; Environmental Monitoring; Environmental Pollutants; Greece; Insect Control; Insecticides; Methomyl; Pesticides; Poisoning; Poisons
PubMed: 30046915
DOI: 10.1007/s10661-018-6838-5 -
Frontiers in Plant Science 2017Arbuscular mycorrhizal fungi (AMF) are crucial components of fertile soils, able to provide several ecosystem services for crop production. Current economic, social and...
Arbuscular mycorrhizal fungi (AMF) are crucial components of fertile soils, able to provide several ecosystem services for crop production. Current economic, social and legislative contexts should drive the so-called "second green revolution" by better exploiting these beneficial microorganisms. Many challenges still need to be overcome to better understand the mycorrhizal symbiosis, among which (i) the biotrophic nature of AMF, constraining their production, while (ii) phosphate acts as a limiting factor for the optimal mycorrhizal inoculum application and effectiveness. Organism fitness and adaptation to the changing environment can be driven by the modulation of mitochondrial respiratory chain, strongly connected to the phosphorus processing. Nevertheless, the role of the respiratory function in mycorrhiza remains largely unexplored. We hypothesized that the two mitochondrial respiratory chain components, alternative oxidase (AOX) and cytochrome oxidase (COX), are involved in specific mycorrhizal behavior. For this, a complex approach was developed. At the pre-symbiotic phase (axenic conditions), we studied phenotypic responses of spores with two AOX and COX inhibitors [respectively, salicylhydroxamic acid (SHAM) and potassium cyanide (KCN)] and two growth regulators (abscisic acid - ABA and gibberellic acid - Ga3). At the symbiotic phase, we analyzed phenotypic and transcriptomic (genes involved in respiration, transport, and fermentation) responses in biosystem (glasshouse conditions): we monitored the effects driven by ABA, and explored the modulations induced by SHAM and KCN under five phosphorus concentrations. KCN and SHAM inhibited spore germination while ABA and Ga3 induced differential spore germination and hyphal patterns. ABA promoted mycorrhizal colonization, strong arbuscule intensity and positive mycorrhizal growth dependency (MGD). In ABA treated plants, induced down-regulation of gene isoforms and up-regulation of genes involved in plant COX pathway. In all phosphorus (P) concentrations, blocking AOX or COX induced opposite mycorrhizal patterns : KCN induced higher -type arbuscule density, positive MGD but lower root colonization compared to SHAM, which favored -type formation and negative MGD. Following our results and current state-of-the-art knowledge, we discuss metabolic functions linked to respiration that may occur within mycorrhizal behavior. We highlight potential connections between AOX pathways and fermentation, and we propose new research and mycorrhizal application perspectives.
PubMed: 28424712
DOI: 10.3389/fpls.2017.00417