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Toxicology Nov 1978Circadian rhythms in mortality and/or survival time following a single intraperitoneal injection of a LD50 of potassium cyanide were studied. In two investigations,...
Circadian rhythms in mortality and/or survival time following a single intraperitoneal injection of a LD50 of potassium cyanide were studied. In two investigations, different but comparable subgroups of inbred male BALB/cCr mice were treated at 4-h intervals (under conditions standardized for chronobiologic study) during 24-h spans. Mice were observed for exact time-to-death during the first hour after treatment as well as overall mortality during the entire 24-h post-injection span following each KCN treatment timepoint. In both studies, mortality from KCN exhibited a 24-h rhythm. Highest mortality occurred in mice injected at 1600 (80% mortality) in Experiment 1 and 2000 (100% mortality) in Experiment II. Lowest mortality occurred at 0400 (40% mortality) in Experiment I and 0800 (30% mortality) in Experiment II. The need to consider the circadian organization of physiologic function when bioassaying toxicity is discussed.
Topics: Animals; Circadian Rhythm; Cyanides; Drug Resistance; Male; Mice; Mice, Inbred BALB C; Potassium Cyanide; Time Factors
PubMed: 734682
DOI: 10.1016/s0300-483x(78)91539-1 -
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 -
Archives of Toxicology Jun 2003The aim of the present study was to determine the effect of the species on the toxicokinetics of cyanide and its main metabolite, thiocyanate. Forty-two rats, six pigs... (Comparative Study)
Comparative Study
The aim of the present study was to determine the effect of the species on the toxicokinetics of cyanide and its main metabolite, thiocyanate. Forty-two rats, six pigs and six goats were dosed orally with 3.0 mg KCN/kg body weight, and cyanide and thiocyanate concentrations in blood were measured within 24 h. After the single oral dose, KCN was rapidly absorbed by rats and goats, with a time of peak concentration ( T(max)) of 15 min. The maximum plasma concentration ( C(max)) of cyanide was observed in goats (93.5 micro mol/l), whereas the C(max) of thiocyanate was higher in rats (58.1 micro mol/l). The elimination half-life ( t(1/2)) and volume of distribution ( Vd(area)) of both cyanide and thiocyanate were higher in goats (1.28 and 13.9 h, and 0.41 and 1.76 l/kg, respectively). Whereas the area under the curve (AUC) of cyanide was significantly higher in goats (234.6 micro mol.l/h), the AUC of thiocyanate was higher in rats (846.5 micro mol.l/h). In conclusion, the results of the present study support the hypothesis that the metabolism of cyanide and its main metabolite, thiocyanate, is species-linked, with the goat being more sensitive to the toxic effects of cyanide/thiocyanate.
Topics: Administration, Oral; Animals; Goats; Male; Pharmacokinetics; Potassium Cyanide; Rats; Rats, Wistar; Species Specificity; Swine; Thiocyanates; Time Factors
PubMed: 12799772
DOI: 10.1007/s00204-003-0446-y -
Toxicology and Applied Pharmacology Sep 1983The excretion of an acute dose of 14C-labeled cyanide in urine, feces, and expired air was studied in rats exposed to daily intake of unlabeled KCN in the diet for 6...
The excretion of an acute dose of 14C-labeled cyanide in urine, feces, and expired air was studied in rats exposed to daily intake of unlabeled KCN in the diet for 6 weeks. Urinary excretion was the main route of elimination of cyanide carbon in these rats, accounting for 83% of the total excreted radioactivity in 12 hr and 89% of the total excreted radioactivity in 24 hr. The major excretion metabolite of cyanide in urine was thiocyanate, and this metabolite accounted for 71 and 79% of the total urinary activity in 12 hr and 24 hr, respectively. The mean total activity excreted in expired air after 12 hr was only 4%, and this value did not change after 24 hr. Of the total activity in expired air in 24 hr, 90% was present as carbon dioxide and 9% as cyanide. When these results were compared with those observed for control rats, it was clear that the mode of elimination of cyanide carbon in both urine and breath was not altered by the chronic intake of cyanide.
Topics: Animals; Carbon Radioisotopes; Cyanides; Male; Potassium Cyanide; Rats; Thiocyanates
PubMed: 6623474
DOI: 10.1016/0041-008x(83)90109-6 -
Veterinary and Human Toxicology Dec 1991The efficacy of orally administered alpha-ketoglutarate (AKG), alone and in combination with n-acetyl-cysteine (NAC), in reducing the lethal effects of injected...
The efficacy of orally administered alpha-ketoglutarate (AKG), alone and in combination with n-acetyl-cysteine (NAC), in reducing the lethal effects of injected potassium cyanide was examined in the mouse. A behavioral scoring system was developed to monitor and measure the signs of toxicity associated with cyanide exposure. AKG significantly reduced the lethality of KCN (6.7 mg/kg ip) in a dose-related manner. The protective effect of AKG was observed if given between 10 and 30 min prior to cyanide exposure. NAC increased the protective effect of AKG but did not alter the time course of protection. AKG alone or in combination with NAC significantly reduced the duration of the toxicity associated with cyanide exposure. This study identifies AKG as an orally effective cyanide antagonist. The protective effect of AKG is enhanced by concomitant administration of NAC. Our work also describes a scoring system which quantifies the signs of toxicity associated with cyanide poisoning.
Topics: Acetylcysteine; Administration, Oral; Animals; Dose-Response Relationship, Drug; Drug Therapy, Combination; Ketoglutaric Acids; Male; Mice; Mice, Inbred ICR; Potassium Cyanide
PubMed: 1808834
DOI: No ID Found -
The Journal of Emergency Medicine Sep 2010Hydroxocobalamin, a precursor of vitamin B12, has a history of use in the prehospital setting in France for cyanide poisoning, particularly that associated with smoke...
Hydroxocobalamin, a precursor of vitamin B12, has a history of use in the prehospital setting in France for cyanide poisoning, particularly that associated with smoke inhalation. Because cyanide poisoning by ingestion is less common than smoke inhalation-associated cyanide poisoning, less information is available on prehospital use of hydroxocobalamin to treat cyanide poisoning by ingestion. This report describes a case of prehospital use of hydroxocobalamin for poisoning by ingestion of cyanide. The case supports the efficacy of hydroxocobalamin for acute cyanide poisoning caused by ingestion of a cyanide salt. No adverse events attributed to hydroxocobalamin were observed.
Topics: Antidotes; Humans; Hydroxocobalamin; Male; Middle Aged; Potassium Cyanide; Suicide, Attempted; Vitamin B Complex
PubMed: 18554843
DOI: 10.1016/j.jemermed.2008.04.040 -
PloS One 2018Cyanide fishing, where a solution of sodium or potassium cyanide is used to stun reef fish for easy capture for the marine aquarium and live fish food trades, continues...
Cyanide fishing, where a solution of sodium or potassium cyanide is used to stun reef fish for easy capture for the marine aquarium and live fish food trades, continues to be pervasive despite being illegal in many countries and destructive to coral reef ecosystems. Currently, there is no easy, reliable and universally accepted method to detect if a fish has been exposed to cyanide during the capture process. A promising non-invasive technique for detecting thiocyanate ions, the metabolic byproduct excreted by exposed fish, has been reported in the literature. In an effort to validate this method, four cyanide exposure studies on Amphiprion ocellaris (common clownfish) were carried out over three years. Fish were either exposed to the same (25 ppm) or twice the concentration (50 ppm) as the previsouly published method. Over 100 water samples of fish exposed to cyanide were analyzed by reverse phase HPLC with a C30 column treated with polyethylene glycol and UV detector operating at 220 nm. No thiocyanate was detected beyond the analytical standards and positive controls prepared in seawater. As an alternate means of detecting thiocyanate, water samples and thiocyanate standards from these exposures were derivatized with monobromobimane (MBB) for LC-MS/MS analysis. Thiocyanate was detected in standards with concentrations as low as 0.6 μg/L and quantified to 1 μg/L, but thiocyanate could not be detected in any of the water samples from fish exposed to cyanide with this method either, confirming the HPLC results. Further, we calculated both the mass balance of thiocyanate and the resultant plausible dosage of cyanide from the data reported in the previously published method. These calculations, along with the known lethal dosage of cyanide, further suggests that the detection of thiocyanate in aquarium water is not a viable method for assessing fish exposure to cyanide.
Topics: Animals; Chromatography, High Pressure Liquid; Coral Reefs; Cyanides; Perciformes; Potassium Cyanide; Seawater; Sodium Cyanide; Thiocyanates
PubMed: 29847597
DOI: 10.1371/journal.pone.0196841 -
The British Journal of Surgery Sep 1964
Topics: Animals; Cyanides; Fibroblasts; Granulation Tissue; Hydrogen-Ion Concentration; In Vitro Techniques; Potassium; Potassium Cyanide; Rabbits; Research; Toxicology; Wound Healing
PubMed: 14222577
DOI: 10.1002/bjs.1800510913 -
Rapid Communications in Mass... May 2011Reactive metabolites are estimated to be one of the main reasons behind unexpected drug-induced toxicity, by binding covalently to cell proteins or DNA. Due to their...
Reactive metabolites are estimated to be one of the main reasons behind unexpected drug-induced toxicity, by binding covalently to cell proteins or DNA. Due to their high reactivity and short lifespan, reactive metabolites are analyzed after chemical trapping with nucleophilic agents such as glutathione or cyanide. Recently, unexplained and uncharacterized methylated reaction products were reported in a human liver microsome based reactive metabolite trapping assay utilizing potassium cyanide as a trapping agent. Here, a similar assay was utilized to produce mono- or dimethylated and further cyanide-trapped reaction products from propranolol, amlodipine and ciprofloxacin, followed by ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC/TOF-MS) and ultra-performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) experiments for their more detailed structural elucidation. Formation of all observed cyanide-trapped products was clearly NADPH-dependent and thus metabolism-mediated. The suggested reaction pathways included N-methylation leading to iminium formation in primary and/or secondary amines preceded by cytochrome P450 (CYP)-mediated reactions. As the methylation reaction was suggested to be involved in formation of the actual reactive iminium ion, the observed cyanide-trapped products were experimental artifacts rather than trapped reactive metabolites. The results stress that to avoid overestimating the formation of reactive metabolites in vitro, this methylation phenomenon should be taken into account when interpreting the results of cyanide-utilizing reactive metabolite trapping assays. This in turn emphasizes the importance of identification of the observed cyano conjugates during such studies. Yet, metabolite identification has a high importance to avoid overestimation of in vitro metabolic clearance in the cases where this kind of metabonate formation has a high impact in the disappearance rate of the compound.
Topics: Amlodipine; Ciprofloxacin; Drug Evaluation, Preclinical; Female; Humans; Isotope Labeling; Male; Metabolomics; Microsomes, Liver; Pharmaceutical Preparations; Potassium Cyanide; Propranolol
PubMed: 21504003
DOI: 10.1002/rcm.5005 -
Environmental Science and Pollution... Jul 2005Little is known about metabolism rates of environmental chemicals by vegetation. A good model compound to study the variation of rates among plant species is cyanide....
BACKGROUND
Little is known about metabolism rates of environmental chemicals by vegetation. A good model compound to study the variation of rates among plant species is cyanide. Vascular plants possess an enzyme system that detoxifies cyanide by converting it to the amino acid asparagine. Knowledge of the kinetic parameters, the half-saturation constant (Km) and the maximum metabolic capacity (vmax), is very useful for enzyme characterization and biochemical purposes. The goal of this study is to find the enzyme kinetics (K(M) and vmax) during cyanide metabolism in the presence of Chinese vegetation, to provide quantitative data for engineered phytoremediation, and to investigate the variation of metabolic rates of plants.
METHODS
Detached leaves (1.0 g fresh weight) from 12 species out of 9 families were kept in glass vessels with 100 mL of aqueous solution spiked with potassium cyanide at 23 degrees C for 28 h. Four different treatment concentrations of cyanide were used, ranging from 0.44 to 7.69 mg CN/L. The disappearance of cyanide from the aqueous solution was analyzed spectrophotometrically. Realistic values of the half-saturation constant (KM) and the maximum metabolic capacity (vmax) were estimated by a computer program using non-linear regression treatments. As a comparison, Lineweaver-Burk plots were also used to estimate the kinetic parameters.
RESULTS AND DISCUSSION
The values obtained for K(M) and vmax varied with plant species. Using non-linear regression treatments, values of vmax and K(M) were found in a range between 6.68 and 21.91 mg CN/kg/h and 0.90 to 3.15 mg CN/L, respectively. The highest vmax was by Chinese elder (Sambucus chinensis), followed by upright hedge-parsley (Torilis japonica). The lowest Vmax was demonstrated by the hybrid willow (Salix matssudana x alba). However, the highest K(M) was found in the water lily (Nymphea teragona), followed by the poplar (Populus deltoides Marsh). The lowest K(M) was demonstrated by corn (Zea mays L.). The values of vmax were normally distributed with a mean of 13 mg CN/kg/h.
CONCLUSIONS
Significant removal of cyanide from aqueous solution was observed in the presence of plant materials without phytotoxicity, even at high doses of cyanide. This gives rise to the conclusion that the Chinese plant species used in this study are all able to efficiently metabolize cyanide, although with different maximum metabolic capacities. A second conclusion is that the variation of metabolism rates between species is small. All these plants had a similar K(M), indicating the same enzyme is active in all plants.
RECOMMENDATIONS AND OUTLOOK
Detoxification of cyanide with trees seems to be a feasible option for cleaning soils and water contaminated with cyanide. For phytoremediation projects, screening appropriate plant species adapted to local conditions should be seriously considered. More chemicals should be investigated to find common principles of the metabolism of environmental chemicals by plants.
Topics: Biodegradation, Environmental; China; Humans; Models, Biological; Plant Leaves; Plants; Potassium Cyanide; Regression Analysis; Soil Pollutants
PubMed: 16137157
DOI: 10.1065/espr2005.05.261