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Cyanide detoxification in cassava for food and feed uses.

Cassava (Manihot esculenta Crantz) is an important tropical root crop providing energy to about 500 million people. The presence of the two cyanogenic glycosides, linamarin and lotaustralin, in cassava is a major factor limiting its use as food or feed. Traditional processing techniques practiced in cassava production are known to reduce cyanide in tubers and leaves. Drying is the most ubiquitous processing operation in many tropical countries. Sun drying eliminates more cyanide than oven drying because of the prolonged contact time between linamarase and the glucosides in sun drying. Soaking followed by boiling is better than soaking or boiling alone in removing cyanide. Traditional African food products such as gari and fufu are made by a series of operations such as grating, dewatering, fermenting, and roasting. During the various stages of gari manufacture, 80 to 95% cyanide loss occurs. The best processing method for the use of cassava leaves as human food is pounding the leaves and cooking the mash in water. Fermentation, boiling, and ensiling are efficient techniques for removing cyanide from cassava peels.

Animal Feed↗

Estimating the hazards of "less hazardous" cigarettes. III. A study of the effect of various smoking conditions on yields of hydrogen cyanide and cigarette tar.

A brand of cigarette with nominal tar and nicotine yields of 4.0 mg and 0.4 mg, respectively, was examined under various machine-smoked conditions that reflect the wide range of human smoking behavior. Three levels of each of five smoking parameters--butt length, puff duration, puff interval, puff volume, and ventilation occlusion--were examined, and the effects on puff number and total particulate matter (TPM) as well as gas phase, particulate phase, and total HCN yields were estimated. Yields of hydrogen cyanide (a ciliatoxic agent) and TPM varied significantly under different smoking conditions. Ventilation occlusion had the most pronounced effect, accounting for 34% of the response variation of TPM yields and 42% of the response variation for total hydrogen cyanide yields. In the survey of available brands, total hydrogen cyanide yields varied from 2 to 233 micrograms/cigarette for the 115 brands tested, a range less than that observed for a single brand smoked under various nonstandard conditions, providing a possible explanation for the previously noted lack of correspondence between HCN yields under standard conditions and levels of thiocyanate in samples of smokers' plasma and saliva. In addition, hydrogen cyanide yields and efficiency of filters in removing HCN were examined under standard smoking conditions. Acetate filters, the most common variety, were found to remove an average of about 14% of the hydrogen cyanide from the mainstream smoke.

Analysis of Variance↗

Cholestatic hepatitis caused by acute gold potassium cyanide poisoning.

INTRODUCTION: Poisoning after oral ingestion of gold potassium cyanide is rarely reported. A case of suicidal ingestion of gold potassium cyanide (potassium dicyanoaurate; CAS# 13967-50-5) is described. CASE REPORT: A 27-year-old man attempted suicide by ingesting 5 mL gold potassium cyanide solution. He developed vomiting, hyperamylasemia, and hepatic dysfunction. Cyanide poisoning was not detected but acute gold toxicity was noted. Pathologic findings of the liver showed centrilobular cholestasis with eosinophilic degeneration. The whole blood and serum gold were 4361 and 6011 microg/L, respectively, and the 24-hour urine gold was 429 microg/d in samples obtained on day 4. CONCLUSION: Gold-induced hepatotoxicity has been seen infrequently in patients receiving gold therapy. Reported agents include sodium aurothiomalate, sodium aurothiopropranol sulfonate, aurothioglucose, aurothiopolypeptide (Auro-detoxin), auric sulfide, and gold thiosulfate, our report adds gold potassium cyanide.

Acute Disease↗

Anaphylaxis in chopped guinea pig lung. III. Effect of carbon monoxide, cyanide, salicylaldoxime, and ionic strength.

The anaphylactic release of histamine from perfused, chopped guinea pig lung is very sensitive to changes in the NaCl concentration of the containing medium, and it is ionic strength rather than particle concentration which is critical. Consequently, in studies with inhibitors care must be taken to avoid inadvertently increasing ionic strength and thereby misinterpreting the cause of the inhibition. Since immune hemolysis exhibits a similar sensitivity to changes in the NaCl concentration of the suspending medium, salicylaldoxime and phlorizin, which prevent the participation of the third component of complement in immune hemolysis, were investigated for their effect on the anaphylactic reaction. Salicylaldoxime is a potent inhibitor of in vitro anaphylaxis in guinea pig lung, but phlorizin is only a weak inhibitor. Potassium cyanide, 1 mM, inhibits the anaphylactic release of histamine most effectively if the duration of contact between the tissue and the cyanide prior to antigen addition is minimal; preincubation of the tissue with cyanide prior to antigen addition results in progressive diminution of inhibition even when there is only minimal loss of cyanide from the containing medium. The anaphylactic release of histamine from perfused whole lungs or suspensions of blood-free chopped lung is not prevented by the cytochrome oxidase inhibitor, carbon monoxide. In addition, 2-heptyl 4 hydroxyquinoline N oxide and malonic acid, which inhibit aerobic metabolism at different sites, do not prevent the reaction. These studies and those with cyanide indicate that the anaphylactic release of histamine in guinea pig lung is not dependent on cytochrome-mediated aerobic metabolism.

Anaphylaxis↗

Sodium nitroprusside and cyanide release: reasons for re-appraisal.

The standard method for estimating cyanide liberated from sodium nitroprusside (SNP) has been colorimetric. Using a cyanide ion-selective electrode technique, it was found that SNP remained unchanged in the presence of whole blood, plasma and washed erythrocytes, no cyanide being detected. Previously reported releases of cyanide from SNP in vivo and in vitro are probably inaccurate. Values obtained could have arisen not from reaction with blood, but from photo-decomposition during the lengthy analysis required by the colorimetric method or during infusion, if the solution was left uncovered. Because of the supposed cyanide hazard, low doses of SNP have been recommended; it may now be possible to revise these.

Colorimetry↗

Effects of cyanide antidotes used with sodium nitroprusside infusions: sodium thiosulphate and hydroxocobalamin given prophylactically to dogs.

Cyanide antidotes were given to dogs before an infusion of sodium nitroprusside 1.5 mg kg-1 for 1 h. Dogs given thiosulphate 75 mg kg-1 had significantly lower plasma and red cell cyanide concentrations while plasma thiocyanate concentrations were significantly increased in comparison with control. These changes were associated with only minimal disturbance of tissue oxygenation. There was no effect on red cell cyanide or thiocyanate concentrations in dogs treated with hydroxocobalamin 1.5 mg kg-1, but plasma cyanide concentrations were significantly greater than in those receiving no antidote although there was less evidence of impaired oxygenation. There was no evidence of a synergistic action between thiosulphate and hydroxocobalamin. The vascular response to nitroprusside was unchanged in the thiosulphate-treated dogs, but was significantly greater in those given hydroxocobalamin. The implications for prophylaxis and treatment of cyanide poisoning following nitroprusside overdose are discussed.

Animals↗

Sodium thiosulphate decreases blood cyanide concentrations after the infusion of sodium nitroprusside.

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.

Adult↗

Fluorometric determination of cyanide in biological fluids and pyridoxal.

Investigations of the physiological disposition of cyanide during thiosulfate therapy has necessitated the development of a convenient and sensitive method for cyanide analysis. A fluorometric method involving the catalytic conversion of pyridoxal to 4-pyridoxylactone was adapted for use with biological fluids by employing microdiffusion analysis. The presence of the cyanide antagonist, sodium thiosulfate, interferes with the formation of the fluorophore. In order to circumvent this interference, the pH of the diffusion media was altered to selectively diffuse cyanide. After testing various acidifying agents, an acetate buffer (pH = 5.2) was determined to be satisfactory. The fluorometric method was then correlated with the classical colorimetric procedure by an in vivo study. Blood from mice treated with sodium nitrite and sodium thiosulfate, prior to receiving potassium cyanide, was analyzed by both procedures and no significant difference was demonstrated between the results of the two methods of analysis.

Animals↗

Abnormal cyanide metabolism in uraemic patients.

BACKGROUND: We previously investigated the factors involved in uraemic neuropathy in patients undergoing regular haemodialysis and found a significant relationship between the severity of vibration sensation impairment and the patients' smoking habits. The administration of methylcobalamin markedly improved the severity of uraemic neuropathy in terms of vibration perception thresholds. We presumed that abnormal cyanide metabolism is involved in the development of uraemic neuropathy. METHODS: Serum levels of thiocyanate (SCN-), the detoxication product of cyanide, were determined in 12 patients with preterminal chronic renal failure (PCRF), 30 patients undergoing regular haemodialysis (HD patients), and 13 healthy volunteers as a control group. Nine of the 30 HD patients were smokers. In addition, in 10 HD patients without smoking habits and 10 non-smoking healthy volunteers, the proportion of each vitamin B12 analogue in total vitamin B12 was estimated. RESULTS: The mean serum SCN- level of the 12 PCRF patients (5.1 +/- 1.5 micrograms/ml) was significantly higher than that of the control (2.8 +/- 0.9 micrograms/ml) (P < 0.01). The mean SCN- level before haemodialysis in the 21 non-smoking HD patients was identical to that in the PCRF group, whereas the level in the nine smoking HD patients (7.2 +/- 1.8 micrograms/ml) significantly higher than that in the non-smoking subgroup (P < 0.01). In 16 HD patients with methylcobalamin treatment, serum SCN- levels were lower than in those without methylcobalamin treatment (4.5 +/- 0.5 micrograms/ml in non-smoking subgroup, P < 0.05). And in the methylcobalamin-treated subgroup (n = 5), the proportion of each vitamin B12 analogue in total vitamin B12 was normal. In the untreated subgroup (n = 5), the proportion of cyanocobalamin fraction (10.5 +/- 2.6%) was as high as the level in Leber's disease patients, while the proportion of methylcobalamin fraction was low. And the serum cyanocobalamin level was higher in the treated subgroup. CONCLUSION: In uraemic patients, cyanide detoxication capability is impaired because of a reduced SCN- clearance, and increased cyanocobalamin synthesis indicates elevation of cyanide pool, which would be related to the development of uraemic neuropathy. Methylcobalamin was considered to be utilized in cyanide detoxication process via cyanocobalamin synthesis.

Adult↗

Characterization of cyanide-resistant respiration and appearance of a 36 kDa protein in mitochondria isolated from antimycin A-treated Hansenula anomala.

Mitochondria exhibiting cyanide-resistant respiration were isolated from Hansenula anomala which had been incubated in the presence of antimycin A to induce cyanide-resistant respiration. The cyanide-resistant respiration in isolated mitochondria was not inhibited by antimycin A or myxothiazol, suggesting that the branching of the pathway from the normal cyanide-sensitive pathway takes place at the coenzyme Q level. Analysis of mitochondrial proteins by sodium dodecyl sulfate gel electrophoresis indicated that a 36 kDa protein was induced by antimycin A treatment of the yeast. It is suggested that this protein is a component of the cyanide-resistant respiratory pathway.

Antifungal Agents↗

PPARalpha-mediated upregulation of uncoupling protein-2 switches cyanide-induced apoptosis to necrosis in primary cortical cells.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a member of the nuclear factor PPAR family that regulates a variety of cellular functions, including lipid metabolism, cellular oxidative stress defense, and inflammatory responses. Based on the report that Wy14,643, a PPARalpha agonist, can upregulate uncoupling protein-2 (UCP-2), this study was conducted in primary cortical cells to determine if PPARalpha activation enhances cyanide-induced neurotoxicity through changes in the level of UCP-2. PCR and Western blot analysis showed that Wy14,643 upregulated UCP-2 transcriptionally over a 12-h period. This response was mediated by PPARalpha since it was blocked by MK886, a selective PPARalpha antagonist. The effect of UCP-2 upregulation on the cytotoxic response to cyanide was quantitated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (apoptosis) and propidium iodide staining (necrosis). Wy14,643 switched the mode of cyanide-induced cell death from apoptosis to necrosis. Cell death was preceded by marked mitochondrial dysfunction, as reflected by depletion of ATP and reduction of the mitochondrial membrane potential (DeltaPsim). Knock down of UCP-2 expression by RNA interference blocked the Wy14,643-mediated enhancement of cyanide-induced mitochondrial dysfunction and the switch of the cell death mode, thus confirming that the response was mediated by upregulation of UCP-2. This study shows that PPARalpha activation can upregulate UCP-2 expression, which in turn enhances cyanide-induced necrotic cell death through an increase of mitochondrial dysfunction.

Animals↗

Cyanide antidotes and methods of their administration in dogs: a comparative study.

To test the efficacies of various antidotes to cyanide (CN) poisoning, the lethal dose of cyanide in dogs was estimated during constant infusion of potassium cyanide at a rate of 0.1 mg/kg/min. Additionally, arterial blood pressure, right ventricular pressure, heart rate, electrocardiogram, blood-gas and pH values, and whole blood and tissue CN concentrations were measured. The lethal dose in animals whose lungs were ventilated with room air was 2.4 +/- .2 mg/kg (mean +/- SE), while the whole-blood CN concentration was 438 +/- 40 micrograms/dl and the gracilis muscle concentration was 2.0 +/- .3 micrograms/100 g. A low dose of vitamin B12a (100 mg/kg), an infusion of thiosulfate (12 mg/kg/h), or ventilation with 100 per cent O2 increased the amount of CN needed to cause death. A bolus injection of nitrite (5 mg/kg), thiosulfate (150 mg/kg), or cysteine (450 mg/kg) increased the the protection from lethality even further. Protection against CN administration for the total 150-min period of observation was provided by a bolus injection plus a constant infusion of nitrite (5 mg/kg bolus plus 5 mg/kg/h). thiosulfate (30 mg/kg bolus plus 60 mg/kg/h), or vitamin B12a (50 mg/kg bolus plus 100 mg/kg/h). However, nitrite infusion produced high levels of methemoglobin 7.2 +/- 1.1 g/dl, while vitamin B12a infusion and cysteine injection, at the stated doses, did not prevent cyanide-induced circulatory failure. Therefore, thiosulfate appears to be the most effective and safest prophylactic agent against cyanide toxicity in dogs.

Amygdalin↗

Cyanide fatalities: case studies of four suicides and one homicide.

Deaths due to cyanide poisoning are relatively rare, largely owing to the restricted availability of cyanide. Nevertheless, the authors report five cases of cyanide fatalities occurring within a few months. Cyanide is one of the most rapidly acting poisons known and is still used for suicide and homicide. The discussion focuses on the circumstances, metabolic changes, pathophysiology, blood levels, diagnosis, and management of cyanide poisoning.

Adult↗

Acute cyanide poisoning.

OBJECTIVE: Cyanide intoxication is an extremely rare event. We report a case of a teenager presenting with unresponsiveness, hemodynamic instability, and profound anion gap metabolic acidosis secondary to elevated lactate levels. It was later confirmed that he was a victim of cyanide poisoning. DESIGN: Individual case report. SETTING: Pediatric intensive care unit of a tertiary care hospital. PATIENT: A 17-yr-old male presented with seizures, apnea, and cardiovascular collapse. His laboratory evaluation revealed extreme anion gap metabolic acidosis, elevated lactate levels, and absent arteriovenous saturation difference. INTERVENTIONS: The patient required inotropic support and external cardiac pacing for hemodynamic instability. Serial measurements of electrolytes and arterial and central venous blood gases were performed. When cyanide poisoning was suspected he received antidote therapy, administered initially with interval dosing and then as a continuous infusion. The antidote infusions were stopped because of a high level of resultant methemoglobinemia and the belief that all ingested cyanide had been cleared, given the time from exposure. The patient never recovered neurologic function, was declared brain dead, and became a tissue and organ donor. CONCLUSION: Cyanide poisoning is a rare and potentially fatal event. Prompt recognition of its possibility in a critically ill patient can lead to early intervention with antidote therapy and decrease the extent of morbidity and mortality.

Acidosis, Lactic↗

The respiratory system of Chromobacterium violaceum grown under conditions of high and low cyanide evolution.

The particulate fraction of disrupted Chromobacterium violaceum grown under cyanide-evolving conditions was unable to oxidize ascorbate plus N,N,N',N'-tetra-methyl-p-phenylenediamine (TMPD), but oxidized NADH and succinate by a linear respiratory pathway which was very resistant to inhibition by cyanide. When the bacteria were grown under conditions where little cyanide evolution occurred, particulate fractions developed the ability to oxidize ascorbate-TMPD by a pathway highly sensitive to cyanide inhibition; respiratory activity with NADH and succinate proceeded via both the cyanide-sensitive and-resistant pathways. Studies with respiratory inhibitors, and the cytochrome compositions of the fractions derived from cultures grown under both conditions, are presented. A soluble, carbon monoxide-binding cytochrome c was found, and this appears similar to those found recently in Beneckea natiegens, methylotrophic bacteria and the marine pseudomonad B16.

Antimycin A↗

Regulation of expression of the cyanide-insensitive terminal oxidase in Pseudomonas aeruginosa.

The regulation of the cyanide-insensitive oxidase (CIO) in Pseudomonas aeruginosa, a bacterium that can synthesize HCN, is reported. The expression of a cioA-lacZ transcriptional fusion, CioA protein levels and CIO activity were low in exponential phase but induced about fivefold upon entry into stationary phase. Varying the O(2) transfer coefficient from 11.5 h(-1) to 87.4 h(-1) had no effect on CIO expression and no correlation was observed between CIO induction and the dissolved O(2) levels in the growth medium. However, a mutant deleted for the O(2)-sensitive transcriptional regulator ANR derepressed CIO expression in an O(2)-sensitive manner, with the highest induction occurring under low-O(2) conditions. Therefore, CIO expression can respond to a signal generated by low O(2) levels, but this response is normally kept in check by ANR repression. ANR may play an important role in preventing overexpression of the CIO in relation to other terminal oxidases. A component present in spent culture medium was able to induce CIO expression. However, experiments with purified N-butanoyl-L-homoserine lactone or N-(3-oxododecanoyl)homoserine lactone ruled out a role for these quorum-sensing molecules in the control of CIO expression. Cyanide was a potent inducer of the CIO at physiologically relevant concentrations and experiments using spent culture medium from a DeltahcnB mutant, which is unable to synthesize cyanide, showed that cyanide was the inducing factor present in P. aeruginosa spent culture medium. However, the finding that in a DeltahcnB mutant cioA-lacZ expression was induced normally upon entry into stationary phase indicated that cyanide was not the endogenous inducer of the terminal oxidase. The authors suggest that the failure of O(2) to have an effect on CIO expression in the wild-type can be explained either by the requirement for an additional, stationary-phase-specific inducing signal or by the loss of an exponential-phase-specific repressing signal.

Bacterial Proteins↗

Cyanide metabolism in motor neuron disease.

Cyanide concentrations in whole blood, saliva and urine were measured in 83 patients with motor neuron disease (MND) and age-, sex-matched control subjects consisting of 62 patients with and 49 without neurological disorders. Cyanide levels in whole blood and urine of MND patients were significantly higher than the non-neurological control groups in smokers and non-smokers. Cyanide levels in whole blood of MND patients were also higher than the neurologic control group in smokers, but not in non-smokers. There was no significant difference between the cyanide level and either the clinical types or degree of disability of MND. The results suggest that MND patients possess a disorder in cyanide metabolism.

Cyanides↗

Effects of acute lethal cyanide intoxication on central dopaminergic pathways.

In rats treated with sodium cyanide (NaCN), 20 mg/kg intraperitoneally, the striatal dopamine (DA) level was decreased within 60 sec. compared to controls injected with NaCl 0.9%. Treatment with NaCN also increased the naturally occurring L-DOPA in the striatum, but not in the other brain regions studied. Decreased DA levels but increased L-DOPA accumulation were also seen in cyanide-treated animals after inhibition of neuronal L-aromatic amino decarboxylase. In rats given a non-lethal dose of NaCN, 2.5 mg/kg intraperitoneally, 30 min. before sacrifice and L-DOPA, 100 mg/kg intraperitoneally, 25 min. before sacrifice, regional L-DOPA levels were not significantly changed, but the striatal DA levels were diminished compared to controls. Decreased DA levels might indicate that cyanide inhibits the synthesis of brain DA. However, both increased L-DOPA and increased accumulation of L-DOPA after neuronal decarboxylase were observed after cyanide. Furthermore, we have earlier reported that lethal doses of NaCN decreased the DA metabolite HVA in the striatum but did not significantly change the oxidatively deaminated metabolite of DA, DOPAC. Inhibition of L-aromatic amino acid decarboxylase appears to play a minor role in causing decreased striatal DA levels. However, our findings might be compatible with cyanide-produced inhibition of the energy-demanding granular uptake and/or release of DA.

Acute Disease↗