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Effect of dietary sodium nitroprusside as a source of cyanide on the selenium status of chicks given diets of varying selenium concentration.

1. The interaction between dietary cyanide, given in the form of sodium nitroprusside (SNP), and selenium has been studied in two experiments with growing chicks from 14 to 38 d of age. 2. In experiment 1, dietary selenium at 10 mg Se/kg reduced growth, food intake and efficiency of utilisation, and increased relative liver size and selenium content. All of these effects were eliminated by the addition of 0.1 g SNP/kg except for liver selenium content, which progressively declined towards control values as SNP was increased to 0.4 g/kg in increments of 0.1 g/kg. At 0.3 g SNP/kg, cyanide toxicity, as judged by decreased growth, reached significance. 3. In experiment 2, similar effects were observed with selenium at 10 mg Se/kg and SNP at 0.3 g/kg, but selenium deficiency was not evident from growth indicators when selenium supplementation of the diet was omitted completely, nor did these indicators suggest that deficiency was induced by cyanide. 4. In both experiments, plasma and liver glutathione peroxidase activity reflected the dietary selenium content. There was an interaction with dietary SNP content. With selenium intake at a toxic level, SNP increased enzyme activity, further evidence of alleviation of selenium toxicity, but when selenium intake was low and normal, SNP decreased activity in liver, an indication that cyanide could induce deficiency. 5. A possible mechanism for alleviation of selenium toxicity is proposed.

Animals↗

Effect of potassium cyanide on behaviour and time to death in possums.

AIM: To assess the sickness behaviours of possums after eating a lethal dose of potassium cyanide. METHOD: Spontaneous behaviour and the time to loss of physical responses were examined. RESULTS: Cyanide ingestion caused a short-lasting period of mild respiratory stimulation. There was no salivation, retching or vomiting. Convulsions occurred in 73% of the possums. After the ingestion of cyanide, the average time to onset of ataxia was 3 minutes, the average time to overall loss of consciousness was 6.5 minutes, and the time to cessation of breathing was 18 minutes. CONCLUSION: Cyanide is a rapid-acting toxin with few undesirable signs from the welfare perspective.

Journal Article↗

High Mitochondrial Activity but Incomplete Engagement of the Cyanide-Resistant Alternative Pathway in Guard Cell Protoplasts of Pea.

The respiratory properties of guard cell protoplasts (GCP) were examined in comparison with those of mesophyll protoplasts (MCP) from the same leaves of pea (Pisum sativum L. cv Arkel). The rates of respiratory O2 uptake by GCP were extremely high (280 [mu]mol mg-1 Chl h-1) and were several times greater than those of MCP. On the other hand, the rates of photosynthetic O2 evolution by GCP were similar to those of MCP. Also on the basis of protoplast volume, the respiratory rates of GCP were higher: more than three times those of MCP. The enzymes of the tricarboxylic acid cycle, per unit protein or unit protoplast volume, had a 2- to 5-fold higher activity in GCP than in MCP, indicating an enrichment of mitochondrial activity in GCP relative to that in MCP. Respiratory inhibitors were used to assess the activity of the cytochrome (cyanide-sensitive) and alternative (cyanide-resistant) pathways in GCP and MCP. The inhibition of respiration by KCN or antimycin A was more in GCP than that in MCP. The marked inhibition of respiratory O2 uptake by salicylhydroxamic acid in the presence of KCN showed the presence of the cyanide-resistant pathway in GCP. The activity of the cyanide-resistant electron transport path constituted only one-third of total respiration in GCP but accounted for two-thirds of respiration in MCP. The alternative pathway was not completely engaged in GCP but reached its full capacity in MCP.

Journal Article↗

Cyanide-insensitive Respiration in Plant Mitochondria.

Pathways of electron transport have been studied in mitochondria isolated from hypocotyls of etiolated mung bean seedlings and skunk cabbage spadices that show cyanide-resistant respiratory activity. The residual flux through cytochrome c oxidase is shown to be small in comparison with the flux through an unidentified alternative oxidase that is known to have a high affinity for oxygen. This alternative oxidase is not a cytochrome. Skunk cabbage and mung bean mitochondria contain cytochromes a and a(3) that have absorption peaks differing slightly from those of animal preparations. A slow oxidation-reduction of cytochrome a(3)-CN has been demonstrated. Cytochromes b undergo oxidation and reduction in the presence of cyanide but play no essential role in the cyanide-resistant pathway. Antimycin inhibits to an extent similar to that of cyanide; the respiratory chain bifurcates on the substrate side of the antimycin-sensitive site. Evidence is presented for the selective inhibition by thiocyanate, alpha, alpha'-dipyridyl, and 8-hydroxyquinoline of the alternative oxidase pathway, which may therefore contain a non-heme iron protein.

Journal Article↗

Promotion of seed germination by cyanide.

Potassium cyanide at 3 mum to 10 mm promotes germination of Amaranthus albus, Lactuca sativa, and Lepidium virginicum seeds. l-Cysteine hydrogen sulfide lyase, which catalyzes the reaction of HCN with l-cysteine to form beta-l cyanoalanine, is active in the seeds. beta-l-Cyanoalanine is the most effective of the 23 alpha-amino acids tested for promoting germination of A. albus seeds. Aspartate, which is produced by enzymatic hydrolysis of asparagine formed by hydrolysis from beta-cyanoalanine, is the second most effective of the 23 amino acids. Uptake of aspartate-4-(14)C is much lower than of cyanide.Radioactive tracer in K(14)CN shows uptake of about 1.5 mumoles of HCN per gram of A. albus and L. sativa seeds after 20 hours of imbibition. Extracts of the seeds gave high (14)C activity in beta-cyanoalanine, asparagine, and aspartate. The acid-hydrolyzed protein extract gave high activity only in aspartate. Tests were negative for free cyanide in the seed. Respiration of the seed is inhibited more than 75% by KCN and by KN(3) at 10 mm. Azide at greater than 1.0 mm inhibits the promotion of germination by cyanides. Neither 0.1 mm KCN nor KN(3) inhibit O(2) consumption, whereas lower concentrations promote germination. It is concluded that the high rate of utilization of cyanide in the reaction to form beta-l-cyanoalanine and the subsequent incorporation into protein limit any inhibition of oxygen consumption. The promotion of seed germination is substrate-limited by asparagine-aspartate, which is required for protein synthesis.

Journal Article↗

Appearance of an Alternate Pathway Cyanide-resistant during Germination of Seeds of Cicer arietinum.

The combined action of the inhibitors antimycin A and cyanide with benzohydroxamic acid indicates the presence of a cyanide-resistant pathway of respiration in chick pea (Cicer arietinum L.) seeds. The appearance of this pathway takes place during germination. During the first 12 hours of germination, the respiration is predominantly cyanide-sensitive, showing after this time a shift to an "alternate" respiration which is sensitive to benzohydroxamic acid, reaching the maximal cyanide resistance between 72 and 96 hours of germination. The appearance of the alternate pathway is initiated by high O(2) concentrations and depends on cytoplasmic protein synthesis, since its appearance is inhibited by cycloheximide but not by chloramphenicol. Actinomycin D has no effect on the appearance of the alternate pathway. Our results indicate, in agreement with other authors, that the branching point is located between the flavoproteins and cytochromes b, probably at the level of ubiquinone, but the possibility of more than one branching point of the electron flow is also considered.

Journal Article↗

Cyanide Inhibition of Acid-induced Growth in Avena Coleoptile Segments.

The comparative effects of metabolic inhibitors on acid- and auxininduced growth in oat (Avena sativa L. var. Victory) coleoptile segments have been examined. Acid (pH 4)-induced growth in both peeled and unpeeled segments is inhibited by 1 millimolar KCN when added at the time of acidification. KCN inhibits total acid-induced growth by 59 and 76%, respectively, in peeled and nonpeeled segments during the first 60 minutes. The growth rate of cyanide-treated tissue drops to zero or near zero in both peeled and nonpeeled segments during this period. Cyanide inhibition of total acid-induced growth in peeled segments at pH 5 is even more severe, amounting to about 80% during the first 60 minutes. The possibility that inhibition by cyanide may be caused by some nonspecific effect of the inhibitor on a process other than respiration, e.g. turgor reduction due to membrane damage, has not been ruled out. Acid-induced growth is also inhibited by 3 millimolar sodium fluoride and by anoxia. In unpeeled segments total pH 4-induced growth is inhibited 73% by sodium fluoride and 38% by anoxia during the 1st hour. Possible corrections to the above inhibition percentages which may be necessary due to the sensitivity of basal growth to inhibitors are discussed. Cyanide was found to inhibit auxin-induced growth much more rapidly than acid-induced growth. These data suggest that acid growth may be dependent on respiratory metabolism but to a lesser degree than is auxin-induced growth. If the acid growth theory of auxin action is correct, it appears that there may be two steps in the growth process which are dependent on respiratory metabolism: (a) auxin-induced proton pumping which is highly sensitive to respiratory inhibitors; and (b) acid-mediated wall loosening which is moderately and perhaps indirectly sensitive to respiratory inhibitors.

Journal Article↗

Alternative path mediated chloride absorption in cyanide-resistant tissues.

The ability of two cyanide-resistant tissues-aged potato slices and fresh preclimacteric banana slices-to take up chloride in the presence of cyanide has been established. Extensive inhibition of chloride uptake by cyanide and chlorbenzhydroxamate together indicates that chloride absorption in the presence of cyanide is supported by respiration mediated by the alternative path. The partial inhibition of respiration-dependent chloride uptake by chlorbenzhydroxamate alone is independent of its effect on the alternative oxidase, and points to inhibition of the transport process per se.

Journal Article↗

Inhibition by adenine derivatives of the cyanide-insensitive electron transport pathway of plant mitochondria.

The effect of benzylaminopurine was studied on cyanide-resistant mitochondria isolated from aged slices of potato tuber (Solanum tuberosum L. var. Bintje). Benzylaminopurine specifically acted on the cyanide-resistant alternative pathway. In the case of succinate oxidation, it mimicked the action of salicylhydroxamic acid and restored a good oxidative phosphorylation. Kinetic analyses showed that inhibitions by benzylaminopurine, salicylhydroxamic acid, and disulfiram occurred at mutually exclusive sites on the alternative pathway. Cyanide-resistant malate oxidation was only partially inhibited by benzylaminopurine and this inhibition occurred for low concentrations of this compound. On the other hand, the oxidation of exogenous NADH remained unaffected.The effects of several adenine derivatives with or without cytokinin activity and that of a purine analog with anticytokinin activity were also studied. The variation in effectiveness to inhibit cyanide-resistant electron transport was: benzylaminopurine and 7-pentylamino-3-methylpyrazolo (4,3 d) pyrimidine (anticytokinin) > alpha-alpha' dimethyl-allyl-adenine > 6-benzoylamino-9-benzylpurine > kinetin > adenine. No correlation was observed between the ability to inhibit the alternative pathway and the biological activity of these compounds. Liposolubility appeared as a major factor for potential inhibitory effect on the alternative pathway.

Journal Article↗

Incorporation of Molecular Oxygen and Water during Enzymatic Oxidation of Cyanide by Pseudomonas fluorescens NCIMB 11764.

Cell extracts (high-speed [150,000 x g] supernatants) from Pseudomonas fluorescens NCIMB 11764 catalyzed the oxidation of cyanide to CO(inf2) (and NH(inf3)). Conversion was both oxygen and NADH dependent, with 1 mol of each being consumed per mol of cyanide degraded. Analysis of (sup13)CO(inf2) by mass spectrometry indicated that one atom each of isotopically labelled oxygen 18 from molecular oxygen and water were incorporated during enzymatic conversion. The results confirm earlier reports of oxygenase-mediated cyanide conversion in this organism. A reaction pathway for cyanide oxidation involving initial monooxygenation followed by hydrolysis of a hypothetical oxygenated intermediate to CO(inf2) (and NH(inf3)) is proposed.

Journal Article↗

Sorption of iron-cyanide complexes on goethite in the presence of sulfate and desorption with phosphate and chloride.

Soils are contaminated with potentially toxic iron-cyanide complexes by some industrial activities. The influence of sulfate on the sorption of the iron-cyanide complexes ferricyanide, [Fe(CN)6]3-, and ferrocyanide, [Fe(CN)6]4-, on goethite was investigated in batch experiments. The experiments were conducted as influenced by pH and varying sulfate/iron-cyanide complex concentration ratios. Furthermore, the desorption of iron-cyanide complexes sorbed on goethite was studied using phosphate and chloride solutions as influenced by pH and anion concentration. Over the whole pH range (pH 3.5 to 8), ferricyanide and sulfate showed similar affinities for the goethite surface. The extent of ferricyanide sorption strongly depended on sulfate concentrations and vice versa. In contrast, ferrocyanide sorption was only decreased (approximately 12%) by sulfate additions at pH 3.5. Ferricyanide was completely desorbed by 1 M chloride, ferrocyanide not at all. Unbuffered phosphate solutions (pH 8.3) desorbed both iron-cyanide complexes completely. Even in 70-fold excess, pH-adjusted phosphate solutions could not desorb ferrocyanide completely at pH 3.5. For ferricyanide we propose a sorption mechanism that is similar to the sulfate sorption mechanism, including outer-sphere and weak inner-sphere surface complexes on goethite. Ferrocyanide appears to form inner-sphere surface complexes. Additionally, we assume that ferrocyanide precipitates probably as a Berlin Blue-like phase at pH 3.5. Hence, ferrocyanide should be less mobile in the soil environment than ferricyanide or sulfate.

Adsorption↗

Comparison of effects of cyanide and acetylcholine on renal hemodynamics and sodium excretion.

The present study compared the effects of acetylcholine to cyanide under the same experimental conditions of renal clearance in anesthetized dogs. Since cyanide is one of the few drugs for which the mechanism of action is known (cytotoxic hypoxia), some insight may be gained into the renal effects of acetylcholine since both produce direct natriuresis and diuresis. Infusion of 0.2 microgram/kg/min of acetylcholine and 12.0 microgram/kg/min of sodium cyanide into the left renal artery resulted in similar effects, i.e., increased fractional excretion of sodium, potassium, calcium, and magnesium. These effects were immediate and ipsilateral. Both agents increased the renal plasma flow to the same extent. In addition, regression plots of the relation between changes in sodium excretion and changes in renal plasma flow were similar for both agents. The pattern of similar renal functional changes suggested that acetylcholine is not a mere renal vasodilator but that its action is also medicated through alterations on direct transport of ions.

Acetylcholine↗

Clinical and CT scan findings in a case of cyanide intoxication.

A 39-year-old man showed a combination of severe parkinsonism and progressive dystonia following attempted suicide with sodium cyanide. Computed tomography (CT) scan showed bilateral lucencies in the putamen and external globus pallidus. The topography of lesions on CT scan closely correlated with the pathological findings described in a previous report of cyanide-induced parkinsonism. This is the first reported case of cyanide intoxication with delayed-onset dystonia.

Adult↗

Effects of 4-dimethylaminophenol, Co2EDTA, or NaNO2 on cerebral blood flow and sinus blood homeostasis of dogs in connection with acute cyanide poisoning.

The effects of the cyanide antidotes DMAP, Co2EDTA, and NaNO2 on cerebral blood flow (CBF) and cerebral blood gases were investigated in connection with acute poisoning of dogs by cyanide. The substances were injected intravenously. Local CBF as measured with thermocouples in the cingulum increased by 100-200% after a non-lethal dose of KCN (1 mg/kg) and by 50% after injection of NaNO2 (15 mg/kg), that oxidized some 20% of the total hemoglobin to ferrihemoglobin. Co2EDTA (10 mg/kg) induced a decrease in local CBF of 30% and in brain temperature of 0.5 degree C. The temperature diminished also after poisoning by KCN, but it rose by 0.15 degree C after the administration of NaNO2. Local CBF and sinus sagittalis blood flow increased by 60-160% for about 15 min, and the brain temperature decreased by 0.4-0.5 degree C when DMAP (3.25 mg/kg) or Co2EDTA (15 mg/kg) was injected 1 min after poisoning by cyanide (4 mg/kg), a dose that always caused respiratory arrest. Immediately after injection of DMAP the brain temperature rose transiently by 0.1-0.2 degree C. Co2EDTA did not exert such an effect. In the sinus sagittalis blood of artificially ventilated animals pCO2 decreased rapidly by 10-20 mmHg after poisoning and approached the initial level after treatment with DMAP or Co2EDTA. The highest value of pO2 was about 80 mmHg and 50 mmHg after injection of DMAP and Co2EDTA, respectively; thereafter pO2 declined to 20 mmHg or 40 mmHg at 20 min. The lactate concentration increased by 60-70% without tendency to return to normal.

Aminophenols↗

Acetylcholinesterase activity in rat brain: effect of acute cyanide intoxication.

Acetylcholinesterase (AChE) activity in the cerebral cortex, cerebellum, hippocampus, hypothalamus, midbrain, pons and medulla oblongata of mature male rats was determined in control and cyanide-treated animals by a spectrophotometric method. Compared with control, cyanide-treated animals showed significant increases in the AChE activity of the cerrebral cortex, hippocampus and midbrain. This finding suggests an involvement of brain AChE in acute cyanide toxicity.

Acetylcholinesterase↗

Cyanide poisoning successfully treated without 'therapeutic methemoglobin levels'.

A 24-year-old woman ingested an unknown amount of potassium cyanide in a suicide attempt. Coma and metabolic acidosis developed. Administration of the Lilly Cyanide Antidote kit (Eli Lilly and Co, Indianapolis) resulted in prompt resolution of symptoms and full recovery. Whole blood cyanide level was 13 micrograms/mL approximately one hour after ingestion. The highest measured methemoglobin level after sodium nitrite administration was 9.2%, demonstrating that attaining a "therapeutic methemoglobin level" of 25% is unnecessary to insure a satisfactory clinical outcome. Because severe hypotension or excessive methemoglobinemia can be caused by the sodium nitrite component of the Lilly kit, only enough to produce an acceptable clinical response should be administered.

Acidosis↗

Cyanide-induced chronic partial asphyxia in vitro: neurochemical abnormalities and reversal by magnesium.

Neuronal cortical cell cultures obtained from fetal mice were subjected to increasing concentrations of sodium cyanide (10-500 microM) for 6 days in order to simulate prolonged partial asphyxia. Various neurochemical assays were performed to determine if certain cell types were preferentially more affected. Choline acetyltransferase activity was reduced significantly from control values at cyanide concentrations greater than 100 microM; there were similar reductions on a percentage basis in high-affinity uptake of beta-alanine and GABA and in clonazepam-displaceable benzodiazepine (BDZ) binding which reflected the neuronal BDZ receptor population. Ro5-4864-displaceable BDZ binding, a nonneuronal marker, was increased significantly. More modest reductions were apparent in specific BDZ binding and in protein content. Although a particular vulnerability of a specific cell type was not demonstrated, there was more neurochemical than morphologic evidence of cellular dysfunction. Co-exposure of the cultures to magnesium along with the highest concentrations of cyanide substantially prevented both neurochemical and morphologic abnormalities. These results lend further support to the concept that excitatory neurotransmitters may be implicated in the neuronal damage produced by hypoxia.

Animals↗

The efficacy of superactivated charcoal in treating rats exposed to a lethal oral dose of potassium cyanide.

Due to the apparent low binding capacity of activated charcoal for potassium cyanide (KCN) in vitro, the use of oral activated charcoal therapy for oral exposure to cyanide compounds is controversial. In our study, rats were given a lethal oral dose of ground granular KCN (35 or 40 mg/kg) in a gelatin capsule followed immediately by either 4 g/kg of superactivated charcoal in a 20% suspension or a similar volume of deionized water. Signs of cyanide toxicosis occurred rapidly, with a mean time to signs of 3.3 and 2.7 minutes in control animals receiving 35 or 40 mg/kg KCN, respectively. All 26 of the control rats showed signs, and all but one in the 35 mg/kg group died within 19 minutes. Only 12 of 26 rats treated with superactivated charcoal showed signs of KCN toxicosis and eight of those animals died. Oral exposure of rats to lethal doses of KCN can be treated effectively by immediate administration of superactivated charcoal.

Administration, Oral↗