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Comparative Biochemistry and... Apr 2010Cyanide is a ubiquitous substance in the environment. Most of the cyanide absorbed by an animal is detoxified by enzymatic combination with sulfur, thus the...
Cyanide is a ubiquitous substance in the environment. Most of the cyanide absorbed by an animal is detoxified by enzymatic combination with sulfur, thus the detoxification process imposes a nutritional cost. In mammals, interactions among nutrients and toxics may influence the composition of the diet and food intake, as a function of positive or negative post-ingestive feedback. The present work aimed to describe the toxic effects of cyanide, and to determine whether cyanide interferes with diet selection in quail (Coturnix coturnix). A toxicological study was performed with 27 female quails that were assigned to three groups that received by gavage 0, 1.0 or 3.0mg of KCN/kg/day, for 7 consecutive days. The diet selection trial was conducted with 20 female quails, that had access to two separate rations: a conventional quail ration and the same ration supplemented with 1% NaSO(4). During the toxicological study, clinical signs of poisoning and death occurred in a quail treated with cyanide. Histological changes were found only in animals dosed with cyanide, and these consisted of mild hepatic periportal vacuolation, an increased number of vacuoles in the colloid of the thyroid glands, and spongiosis in the mesencephalon. No clinical signs were found in any quail throughout the diet selection trial. There were no significant differences in food consumption or ration preference. In conclusion, exposure to cyanide promotes damage to the liver and central nervous system in quails. In contrast, the ingestion of sulfur by quail was not affected by exposure to cyanide.
Topics: Animal Feed; Animals; Body Weight; Central Nervous System; Coturnix; Diet; Dose-Response Relationship, Drug; Eating; Female; Food Preferences; Liver; Potassium Cyanide; Random Allocation; Toxicity Tests, Acute
PubMed: 19969102
DOI: 10.1016/j.cbpc.2009.12.001 -
Clinical Toxicology (Philadelphia, Pa.) Jan 2020Cyanide is a metabolic poison used in multiple industries and is a high threat chemical agent. Current antidotes require intravenous administration, limiting their...
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. 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. 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). 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 ( = 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 ( ≤ 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. Sodium tetrathionate significantly improves survival and clinical outcomes in a large, swine model of acute cyanide poisoning.
Topics: Animals; Antidotes; Cyanides; Disease Models, Animal; Female; Injections, Intramuscular; Swine; Tetrathionic Acid
PubMed: 31008657
DOI: 10.1080/15563650.2019.1602272 -
Pharmacological Reports : PR 2005Cytoplasm of mammalian glial cells was reported to contain Gomori-positive cytoplasmic granulation (GPCG), whose biological role is unknown. The present study attempted...
Cytoplasm of mammalian glial cells was reported to contain Gomori-positive cytoplasmic granulation (GPCG), whose biological role is unknown. The present study attempted to discover conditions facilitating GPCG formation and to elucidate their relationship with sulfane sulfur metabolism. To address these problems, we investigated in vivo the effect of both allyl disulfide (DADS), occurring in garlic (sulfane sulfur donor) and cyanide (sulfane sulfur acceptor) on number of GPCG-containing glial cells in the mouse brain. In parallel, sulfane sulfur level and activity of rhodanese and 3-mercaptopyruvate sulfurtransferase (MpST) were determined in the mouse brain and liver. Cyanide caused a drop in GPCG number in the brain, while activity of sulfurtransferases and sulfane sulfur level remained unchanged. Slight but significant cyanide-induced rise in MpST activity was observed only in the liver, which indicates a possibility of enhancement of its detoxification in reaction with mercapropyruvate in this organ. DADS, a sulfur donor, increased GPCG number in the brain, whereas activity of sulfurtransferases and sulfane sulfur level did not change. However, in the liver, DADS elevated both sulfurtransferase activity and sulfane sulfur level. These observations suggest that DADS can constitute a source of sulfane sulfur for the liver, thereby activating anaerobic sulfur metabolism and sulfane sulfur transfer. Consequently, this leads to the increase in sulfane sulfur level in plasma, in which it is transported in the form of albumin hydropersulfides and can be used for cyanide detoxification or stored in glial cells as GPCG. Therefore, it is not excluded that GPCG observed in the brain of mice and other mammals can be a source and a store of sulfane sulfur in mammals.
Topics: Allyl Compounds; Animals; Brain; Cytoplasmic Granules; Disulfides; Female; Liver; Mice; Neuroglia; Potassium Cyanide; Sulfur Compounds; Sulfurtransferases
PubMed: 15886420
DOI: No ID Found -
British Journal of Anaesthesia Feb 1979The cardiovascular and acid-base changes following equivalent i.v. bolus doses of sodium nitroprusside (SNP) and potassium cyanide (KCN) have been studied in two groups...
The cardiovascular and acid-base changes following equivalent i.v. bolus doses of sodium nitroprusside (SNP) and potassium cyanide (KCN) have been studied in two groups of anaesthetized dogs. In a third group, the metabolic changes produced by i.v. infusion of SNP 1.5 mg kg-1 at a constant rate over 1 h have been studied. In contrast to a decrease in arterial pressure following SNP, hypertension and tachycardia occurred after the administration of KCN, with hyperventilation and an increase in packed cell volume. During infusion of SNP, increases in plasma cyanide concentrations were associated with an increase in arterial base deficit, plasma lactate and excess lactate and a decrease in oxygen consumption. The occurrence of lactic acidosis with SNP 1.5 mg kg-1 suggests that this may be the maximum safe dose for short term infusion. However, all these changes reversed spontaneously following discontinuation of SNP, indicating that base deficit is an adequate metabolic monitor during administration of SNP.
Topics: Acid-Base Equilibrium; Animals; Cyanides; Dogs; Ferricyanides; Hemodynamics; Lactates; Nitroprusside; Oxygen Consumption; Potassium Cyanide; Time Factors
PubMed: 426997
DOI: 10.1093/bja/51.2.81 -
Anesthesiology Sep 1996During fire exposure, cyanide toxicity can block aerobic metabolism. Oxygen and sodium thiosulfate are accepted therapy. However, nitrite-induced methemoglobinemia,...
BACKGROUND
During fire exposure, cyanide toxicity can block aerobic metabolism. Oxygen and sodium thiosulfate are accepted therapy. However, nitrite-induced methemoglobinemia, which avidly binds cyanide, decreases oxygen-carrying capacity that is already reduced by the presence of carboxyhemoglobin (inhalation of carbon monoxide in smoke). This study tested whether exogenous stroma-free methemoglobin (SFmetHb) can prevent depression of hemodynamics and metabolism during canine cyanide poisoning.
METHODS
In 10 dogs (weighing 18.8 +/- 3.5 kg) anesthetized with chloralose-urethane and mechanically ventilated with air, baseline hemodynamic and metabolic measurements were made. Then, 137 +/- 31 ml of 12 g% SFmetHb was infused into five dogs (SFmetHb group). Finally, the SFmetHb group and the control group (n = 5, no SFmetHb) received an intravenous potassium cyanide infusion (0.072 mg.kg-1.min-1) for 20 min. Oxygen consumption (VO2) was measured with a Datex Deltatrac (Datex Instruments, Helsinki, Finland) metabolic monitor and cardiac output (QT) was measured by pulmonary artery thermodilution.
RESULTS
From baseline to cyanide infusion in the control group, QT decreased significantly (p < 0.05) from 2.9 +/- 0.8 to 1.5 +/- 0.4 l/min, mixed venous PCO2 (PvCO2) tended to decrease from 35 +/- 4 to 23 +/- 2 mmHg, PvO2 increased from 43 +/- 4 to 62 +/- 8 mmHg, VO2 decreased from 93 +/- 8 to 64 +/- 19 ml/min, and lactate increased from 2.3 +/- 0.5 to 7.1 +/- 0.7 mM. In the SFmetHb group, cyanide infusion did not significantly change these variables. From baseline to infused cyanide, the increases in blood cyanide (4.8 +/- 1.0 to 452 +/- 97 microM) and plasma thiocyanate cyanide (18 +/- 5 to 65 +/- 22 microM) in the SFmetHb group were significantly greater than those increases in the control group. SFmetHb itself caused no physiologic changes, except small decreases in heart rate and PvO2. Peak SFmetHb reached 7.7 +/- 1.0% of total hemoglobin.
CONCLUSIONS
Prophylactic intravenous SFmetHb preserved cardiovascular and metabolic function in dogs exposed to significant intravenous cyanide. Blood concentrations of cyanide, and its metabolite, thiocyanate, revealed that SFmetHb trapped significant cyanide in blood before tissue penetration.
Topics: Animals; Dogs; Methemoglobin; Oxygen Consumption; Potassium Cyanide
PubMed: 8853086
DOI: 10.1097/00000542-199609000-00015 -
Veterinary Research 2003The present work was aimed at evaluating the effects of maternal exposure to potassium cyanide (KCN) during lactation in goats. Twenty-seven lactating female goats were...
The present work was aimed at evaluating the effects of maternal exposure to potassium cyanide (KCN) during lactation in goats. Twenty-seven lactating female goats were orally dosed with 0 (control), 1.0, 2.0, or 3.0 mg KCN/kg body weight/day from lactation days 0 to 90. After this period, all male kids and one mother from each group were killed for a pathological study. Cyanide treatment promoted the clinical signs of maternal toxicity in the highest KCN group but did not affect body weight. Both cyanide and thiocyanate presented increased levels in both dams and kids from the treated groups. Microscopic lesions, but without alterations on the biochemical panel, were found in the brain, thyroid, liver, and kidneys of both dams and kids from the treated groups. These findings suggest that lactating offspring can be indirectly intoxicated by maternal exposure to cyanide.
Topics: Animals; Animals, Suckling; Brain; Brain Chemistry; Female; Goats; Kidney; Lactation; Liver; Male; Maternal Exposure; Milk; Potassium Cyanide; Thiocyanates; Thyroid Gland; Time Factors
PubMed: 12657213
DOI: 10.1051/vetres:2002068 -
British Journal of Anaesthesia Feb 1979Blood cyanide (HCN) and thiocyanate (SCN) concentrations were measured at intervals in anaesthetized dogs given bolus doses of sodium nitroprusside (SNP) 1 mg kg-1 or...
Blood cyanide (HCN) and thiocyanate (SCN) concentrations were measured at intervals in anaesthetized dogs given bolus doses of sodium nitroprusside (SNP) 1 mg kg-1 or potassium cyanide 1.07 mg kg-1 and in animals infused with SNP 1.5 mg kg-1 for 1 h. Cyanide appeared rapidly in the red cells to give peak concentrations which accounted for more than 90% of the total blood HCN. A delay between the peak plasma and red cell HCN concentrations confirmed that some of the SNP was degraded in the plasma. Comparison of HCN and SCN concentrations with those measured previously in patients receiving an infusion of SNP suggests that the degradation of SNP and detoxication of HCN may be more rapid in the dog. The various pathways of HCN detoxication are discussed in relation to the reduced formation of SCN in dogs receiving SNP compared with those receiving KCN.
Topics: Animals; Cyanides; Dogs; Erythrocytes; Ferricyanides; Nitroprusside; Potassium Cyanide; Thiocyanates; Time Factors
PubMed: 426998
DOI: 10.1093/bja/51.2.89 -
Shock (Augusta, Ga.) Mar 2017Our objective was to determine how circulatory failure develops following systemic administration of potassium cyanide (KCN). We used a noninhaled modality of...
Our objective was to determine how circulatory failure develops following systemic administration of potassium cyanide (KCN). We used a noninhaled modality of intoxication, wherein the change in breathing pattern would not influence the diffusion of CN into the blood, akin to the effects of ingesting toxic levels of CN. In a group of 300 to 400 g rats, CN-induced coma (CN i.p., 7 mg/kg) produced a central apnea within 2 to 3 min along with a potent and prolonged gasping pattern leading to autoresuscitation in 38% of the animals. Motor deficits and neuronal necrosis were nevertheless observed in the surviving animals. To clarify the mechanisms leading to potential autoresuscitation versus asystole, 12 urethane-anesthetized rats were then exposed to the lowest possible levels of CN exposure that would lead to breathing depression within 7 to 8 min; this dose averaged 0.375 mg/kg/min i.v. At this level of intoxication, a cardiac depression developed several minutes only after the onset of the apnea, leading to cardiac asystole as PaO2 reached value approximately 15 Torr, unless breathing was maintained by mechanical ventilation or through spontaneous gasping. Higher levels of KCN exposure in 10 animals provoked a primary cardiac depression, which led to a rapid cardiac arrest by pulseless electrical activity (PEA) despite the maintenance of PaO2 by mechanical ventilation. These effects were totally unrelated to the potassium contained in KCN. It is concluded that circulatory failure can develop as a direct consequence of CN-induced apnea but in a narrow range of exposure. In this "low" range, maintaining pulmonary gas exchange after exposure, through mechanical ventilation (or spontaneous gasping), can reverse cardiac depression and restore spontaneous breathing. At higher level of intoxication, cardiac depression is to be treated as a specific and spontaneously irreversible consequence of CN exposure, leading to a PEA.
Topics: Animals; Apnea; Blood Gas Analysis; Cyanides; Male; Potassium Chloride; Pulmonary Gas Exchange; Rats; Rats, Sprague-Dawley; Shock
PubMed: 27513083
DOI: 10.1097/SHK.0000000000000732 -
Journal of Biochemistry Jan 1985Spectral changes of hemoproteins in the near ultraviolet region on binding to a ligand and on oxidation-reduction of the heme-iron were studied by computer-controlled...
Spectral changes of hemoproteins in the near ultraviolet region on binding to a ligand and on oxidation-reduction of the heme-iron were studied by computer-controlled spectrophotometry. Near ultraviolet difference spectra between the low spin and high spin forms of ferric hemoproteins were classified into three groups: Those showing two absorption peaks having maxima at around 285 and 295 nm, those showing a peak at around 275 nm, and those showing a peak at around 300 nm. No corresponding absorption peak was observed with model heme complexes of low molecular weight. The intensity of the peak in cyanide difference spectra of catalase and horseradish peroxidase in the near ultraviolet region was dependent on the concentration of added cyanide and paralleled the intensity of the spectral changes in the Soret region. The spectral changes in both the near ultraviolet and Soret regions developed within 6 ms after the addition of cyanide. Difference spectra between the reduced and oxidized forms of cytochrome c, cytochrome oxidase-cyanide complex, hemoglobin, and lactoperoxidase-cyanide complex showed a characteristic peak at around 285-290 nm. Various difference spectra of hemoglobin in the near ultraviolet region were also measured. The observed positions, shapes, combinations, and relative intensities of the peaks were compared with those of solvent perturbation difference spectra and pH difference spectra of proteins and aromatic amino acids and also with the diacetylchitobiose-induced difference spectrum of lysozyme. The kinds of aromatic amino acid residues possibly responsible for the observed difference peaks were discussed on the basis of the results of the comparison. Based on the results obtained, the common occurrence of a heme-linked functional response of the hemoprotein conformation was suggested.
Topics: Animals; Catalase; Cattle; Cytochrome P-450 Enzyme System; Electron Transport Complex IV; Ferric Compounds; Heme; Hemeproteins; Hemoglobins; Horseradish Peroxidase; Humans; Lactoperoxidase; Methemoglobin; Muramidase; Nitrite Reductases; Oxidation-Reduction; Potassium Cyanide; Spectrophotometry; Spectrophotometry, Ultraviolet; Swine
PubMed: 2987198
DOI: 10.1093/oxfordjournals.jbchem.a135052 -
BMC Pharmacology & Toxicology Mar 2017Better and safer antidotes against cyanide poisoning are needed. Prior study has shown a favorable effect of isosorbide dinitrate (ISDN) on the survival of...
BACKGROUND
Better and safer antidotes against cyanide poisoning are needed. Prior study has shown a favorable effect of isosorbide dinitrate (ISDN) on the survival of cyanide-poisoned rabbits when administered as early as 1 min after poisoning. The aim of the current study was to further evaluate the efficacy of intravenous ISDN administered in clinically relevant timing for first responders.
METHODS
A comparative animal study using 24 rabbits in 4 randomized study groups was performed. Animals were poisoned with intravenous potassium cyanide (1 mg/kg). Animals in Group 1 served as controls and received no treatment. Groups 2-4 animals were treated intravenously with ISDN (50 μg/kg) after poisoning; one group after 3 min, another group after 5 min and the last after 7 min. Animals were observed for 30 min after poisoning. The study endpoints included survival rate, clinical status, blood pressure, pulse per minute, blood lactate and pH.
RESULTS
Five of 6 animals (83.3%) from every treatment group survived the whole observation period while all control untreated animals died. All the rabbits collapsed immediately after exposure, showing rapidly deteriorated vital signs with lactic metabolic acidosis (peak blood lactate levels of 18.1 to 19.0 mmol/L on average at 10 min post exposure). Vital signs, clinical scores, and blood gases of treated rabbits gradually improved.
CONCLUSION
Poisoned rabbits showed improved short-term survival following the administration of ISDN up to 7 min after lethal cyanide poisoning of. We see a potential for ISDN as an antidote against cyanide poisoning.
Topics: Administration, Intravenous; Animals; Drug Administration Schedule; Isosorbide Dinitrate; Poisoning; Potassium Cyanide; Rabbits; Random Allocation; Survival Rate; Treatment Outcome; Vasodilator Agents
PubMed: 28288687
DOI: 10.1186/s40360-017-0122-0