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Cytochrome abnormalities and cyanide-resistant respiration in extranuclear mutants of Aspergillus nidulans.

The cytochrome spectra of two extranuclear mutants of Aspergillus nidulans and the double-mutant recombinant formed from them have been examined both at room temperature and at the temperature of liquid N2 and compared with those of the wild-type strain. The oligomycin-resistant, slow growing mutant contained an increased amount of cytochrome c without any loss of cytochromes b and a,a3. The cold-sensitive mutant, apparently normal when grown at 37 C, showed an increased amount of cytochrome c and a partial loss of cytochromes b and a,a3 when grown at 20 C. A combination of these effects was observed in the double-mutant recombinant. Cyanide-resistant respiration was present in both mutant strains and in the recombinant at much higher levels than in the wild-type strain. In the oligomycin-resistant mutant, this was usually present together with cyanide-sensitive respiration, whereas in the cold-sensitive mutant and recombinant grown at 20 C cyanide-resistant approached 100%. Inhibitor and growth yield studies indicated that the cyanide-resistant pathway was not used by the cold-sensitive mutant during growth at 20 C.

Antimycin A↗

Delayed cyanide poisoning following acetonitrile ingestion.

Acetonitrile (methyl cyanide) is a common industrial organic solvent but is a rare cause of poisoning. We report the first recorded UK case. Acetonitrile is slowly converted to cyanide, resulting in delayed toxicity. We describe a case of deliberate self-poisoning by a 39-year-old woman resulting in cyanide poisoning 11 hours later which was successfully treated by repeated boluses of sodium nitrite and thiosulphate. The half-life of conversion of acetonitrile was 40 hours and harmful blood cyanide levels persisted for over 24 hours after ingestion. Departments treating or advising in cases of poisoning need to be aware of the delayed toxicity of acetonitrile. Monitoring in an intensive care unit of cases of acetonitrile poisoning should continue for 24-48 hours.

Acetonitriles↗

Dissociation of adrenocortical secretory responses to cyanide and philocarpine in dogs with hypothalamic lesions.

In dogs with hypothalamic lesions as well as in intact and hypophysectomized dogs, adrenal venous blood samples were collected and analyzed for 17-hydroxycorticosteroids (17-OHCS). In intact dogs a marked increase in adrneal 17-OHCS secretion was observed following the i.v. infusion of cyanide as well as after the i.v. injection of pilocarpine; this was completely abolished by hypophysectomy. The adrenocortical response to pilocarpine was markedly impaired and that to cyanide partially suppressed after lesioning of the anterior median eminence. However, after lesioning of the posterior median eminence, the adrenocortical secretory response to pilocarpine was almost the same as in intact dogs, whereas the response to cyanide was markedly impaired. Thus, a dissociation of adrenocortical secretory responses to cyanide and pilocarpine was demonstrated in dogs with hypothalamic lesions.

17-Hydroxycorticosteroids↗

Adrenal cortical secretory responses to histamine and cyanide in dogs with hypothalamic lesions.

Experiments were performed on dogs with hypothalamic lesions as well as on intact and hypophysectomized dogs. Adrenal venous blood samples were collected and analyzed for 17-hydroxycorticosteroids (17-OHCS). In intact dogs, a marked increase in adrenal 17-OHCS secretion was observed after an i.v. injection of histamine and following an i.v. infusion of cyanide. Adrenal 17-OHCS secretion in response to histamine was markedly reduced but not completely abolished by hypophysectomy and was partially impaired by anterior median eminence lesions and by posterior median eminence lesions, but was not significantly impaired by supramammillary lesions. Adrenal 17-OHCS secretion in response to cyanide was completely abolished by hypophysectomy, markedly reduced by posterior median eminence lesions and partially impaired by anterior median eminence lesions and by supramammillary lesions. Thus, a partial dissociation of the adrenocortical secretory responses to histamine and cyanide was observed in dogs with hypothalamic lesions, suggesting that the mechanism and the pathway to the anterior pituitary involved in the adrenocortical secretory response to histamine and cyanide are somewhat different.

17-Hydroxycorticosteroids↗

Mechanisms regulating the cardiac output response to cyanide infusion, a model of hypoxia.

When tissue metabolic changes like those of hypoxia were induced by intra-aortic infusion of cyanide in dogs, cardiac output began to increase after 3 to 5 min, reached a peak (220% of the control value) at 15 min, and returned to control in 40 min. This pattern of cardiac output rise was not altered by vagotomy with or without atropine pretreatment. However, this cardiac output response could be differentiated into three phases by pretreating the animals with agents that block specific activities of the sympatho-adrenal system. First, ganglionic blockade produced by mecamylamine or sympathetic nerve blockade by bretylium abolished the middle phase of the cardiac output seen in the untreated animal, but early and late phases still could be discerned. Second, beta-adrenergic receptor blockade produced by propranolol shortened the total duration of the cardiac output rise by abolishing the late phase. Third, when given together, propranolol and mecamylamine (or bretylium) prevented most of the cardiac output rise that follows the early phase. When cyanide was given to splenectomized dogs, the duration of the cardiac output response was not shortened, but the response became biphasic, resembling that seen after chemical sympathectomy. A similar biphasic response of the cardiac output also resulted from splenic denervation; sham operation or nephrectomy had no effect on the monophasic pattern of the normal response. Splenic venous blood obtained from cyanide-treated dogs, when infused intraportally, caused an increase in cardiac output in recipient dogs; similar infusion of arterial blood had no effects. THESE RESULTS SUGGEST THAT THE CARDIAC OUTPUT RESPONSE TO CYANIDE INFUSION CONSISTS OF THREE COMPONENTS: an early phase, related neither to the autonomic nervous system nor to circulating catecholamines; a middle phase, caused by a nonadrenergic humoral substance released from the spleen by sympathetic stimulation; and a late phase, dependent upon adrenergic receptors but not upon sympathetic transmission.

Animals↗

Promising role of alpha-ketoglutarate in protecting against the lethal effects of cyanide.

Treatment of cyanide poisoning generally includes amyl nitrite and/or sodium nitrite (SN) in combination with sodium thiosulphate (STS). However, in many instances of cyanide poisoning, use of nitrites is contraindicated due to their strong vasoactive properties. alpha-Ketoglutarate (alpha-KG) antagonizes cyanide poisoning by cyanohydrin formation. Protective efficacy of graded doses of alpha-KG (p.o.) as pretreatment, simultaneous treatment or post-treatment was evaluated against acute potassium cyanide (KCN) poisoning (p.o.) in female rats. Pretreatment with alpha-KG (0.125-2.0 g/kg) exhibited dose- and time-dependent effects and was found to be effective even when given up to 60 min prior to KCN. Addition of STS significantly enhanced the protective efficacy of alpha-KG at all the doses and time intervals. A 10-min pretreatment with alpha-KG increased the LD50 of KCN by 7-fold, which was further increased 28-fold by the addition of both SN and STS. Simultaneous treatment with alpha-KG (2.0 g/kg) increased the LD50 of KCN by 7-fold, which was doubled by the addition of STS. However, addition of SN did not confer any additional protection. Post-treatment with alpha-KG + STS minimized the mortality by 50% but did not significantly extend the survival time in KCN (2 LD50)-administered rats. KCN (0.75 LD50) inhibited rat brain cytochrome oxidase, which was significantly protected by pretreatment or simultaneous treatment with alpha-KG and STS. Considering the efficacy and safety of peroral alpha-KG, a promising treatment regimen consisting of alpha-KG + STS or alpha-KG + SN + STS is proposed depending upon the situation.

Animals↗

Spontaneous generation of reactive oxygen species in the mixture of cyanide and glycerol.

Reactive oxygen species are involved in tumor promotion or apoptosis. In assaying prooxidant or antioxidant activities, cyanide has been commonly used as an inhibitor of mitochondrial oxidases, peroxidases, or Cu,Zn-superoxide dismutase, which have an influence on intracellular levels of reactive oxygen species. It has also been used to chemically mimic hypoxia. On the other hand, glycerol has been widely used as a stabilizer of various enzymes. In particular, glycerol is required to maintain the enzymatic activities of membrane-bound NAD(P)H oxidases extracted from surrounding phospholipids. Since both cyanide and glycerol are relatively inert, they have been used concomitantly regardless of any mutual interference. In this study, we demonstrate that a mixture of glycerol and cyanide reduced cytochrome c and nitroblue tetrazolium, both of which are superoxide anion indicators. The mixture also enhanced the production of superoxide anion in the presence of redox-cycling compounds. Superoxide production by the mixture was confirmed by electron spin resonance spectra. Moreover, the mixture induced lipid peroxidation and hemolysis in human erythrocytes. These results suggest that cyanide and glycerol should be used carefully in reaction systems used to measure superoxide production or antioxidant activity. However, sucrose and sodium azide in combination do not produce such artifacts and thus may be used as an alternative.

Cyanides↗

Limitations of the cyanide electrode for use in plasma and whole blood.

Although the cyanide ion-specific electrode has been used for the measurement of cyanide in biologic fluids, its validity has not been documented under these conditions. Therefore, we analyzed 60 paired samples of blood and plasma in a blinded fashion and compared the cyanide ion concentrations obtained from the ion-specific electrode with those obtained from a standard chemical assay. There was poor correlation between results in plasma samples (r = .52, n = 26) and no correlation in whole blood (r = .02, n = 34). Until refinements of the electrode technique are made, this method cannot be recommended for the measurement of cyanide in biologic fluids.

Animals↗

Inhibition by cyanide of drug oxidations in rat liver microsomes.

Cyanide inhibited microsomal activities of aniline hydroxylation and aminopyrine, ethylmorphine and codeine demethylations and produced a modified type II difference spectrum of cytochrome P-450 to give two spectral dissociation constants, 0.21mM and 1.05 mM. The binding of cyanide to cytochrome P-450 resulted in innhibition of NADPH-cytochrome P-450 reductase activity. The cyanide inhibition of drug oxidations was partially avoided by increasing oxygen tension. A possible mechanism for the inhibition of drug oxidations by cyanide is discussed.

Aminopyrine↗

High-sensitivity analysis of cyanide by capillary electrophoresis with fluorescence detection.

A capillary electrophoretic method for a high-sensitivity analysis of cyanide has been developed. Cyanide was derivatized with 2,3-naphthalenedialdehyde and taurine to give a fluorescent product of 1-cyanobenz[f]isoindole. This compound was detected with high sensitivity by fluorescence detection. The detection limit was 0.1 ng/mL, and the calibration curve was linear over the range 0.1-200 ng/mL. The precision of the migration time of within-run assays (n = 6) of 1 ng/mL cyanide standard solution was 0.14%. The precision of the peak area for the same runs was 1.0%. This method was applicable to blood analysis. Detection of the cyanide derivative by UV was also examined.

Blood Chemical Analysis↗

Novel sensitive spectrophotometric method for the trace determination of cyanide in industrial effluent.

The high toxicity of the cyanide ion at low concentration necessitates its analysis in a variety of environmental samples with a very low cyanide content. A new sensitive spectrophotometric method has been developed for the trace determination of cyanide with ninhydrin (NH) in an alkaline medium. Beer's law is obeyed in the range of cyanide concentration 0.04-0.24 microg cm(-3), and the molar absorptivity at 590 nm is 2.20 x 10(5) dm3 mol(-1) cm(-1). The Sandell's sensitivity of the product is 0.000118 microg cm(-2). The optimum reaction conditions and other important analytical parameters have been investigated. The results obtained by using the proposed method for environmental samples agree well with those obtained by the Aldridge standard method.

Cyanides↗

Cyanide removal from wastewater using gas membranes: pilot-scale study.

Results are presented for the removal of cyanide from four different wastewaters using hollow-fiber gas membranes. The pilot-scale membrane facility had a maximum treatment capacity of 1000 L using 10 hollow-fiber modules with a total membrane surface area of 180 m2. The results are in general agreement with previous laboratory-scale studies. However, different wastewaters contain different dissolved solutes. These dissolved solutes reduce the predicted efficiency of the cyanide removal process and the purity of the recovered cyanide. Other volatile species present in the wastewater could be removed with the cyanide into the strip solution. Further osmotic pressure differences between the wastewater and strip solution could lead to water vapor passing through the gas-filled pores of the microporous hollow-fiber membranes.

Cyanides↗

Red cell granules: a new bio-absorbent for absorbing cyanide.

Granules of bovine and human red cells with a diameter about 4 mm and containing methemoglobin inside the cells were prepared artificially. These methemoglobin-containing red cell granules were very effective for detecting and absorbing cyanide in water. Each one g of red cell granules (wet weight) absorbed about 4 mg cyanide within an hour. An instant detector for cyanide was also devised by applying and gelling methemoglobin-containing red cells onto a filter paper. The granules may be useful for absorbing cyanide, which is used in large amounts in gilding factories and detoxified in water through complicated treatment systems.

Absorption↗

Combined antidotal and hemodialysis treatments for nitroprusside-induced cyanide toxicity.

A case report is presented for a patient with nitroprusside-induced cyanide intoxication. The patient received approximately 1 g sodium nitroprusside through an intravenous infusion of the drug over 6 d. The toxicity was treated with antidotes, sodium nitrite and sodium thiosulfate, followed by hemodialysis. Hemodialysis significantly removed thiocyanate but not cyanide from the patient's extracorporeal circulation. The removal of thiocyanate by hemodialysis enhanced the liberation of cyanide from the cytochrome oxidase. Hemodialysis is a significant addition to the therapy of cyanide toxicity, particularly for intoxicated patient with reduced renal function

Cyanides↗

Comparison of nitrite treatment and stroma-free methemoglobin solution as antidotes for cyanide poisoning in a rat model.

The standard nitrite/thiosulfate regimen for cyanide poisoning was tested in our rat model. By modifying the treatment regimen and the nitrite solution an effective antidote against an LD90 of cyanide could be produced. However, this treatment was effective against two times the LD90 only when administered ten minutes prior to cyanide injection. These results are in marked contrast to our results with stroma-free methemoglobin solutions (SFMS) which showed SFMS to be a highly effective antidote against four times the LD90 when administered 30 seconds after an intravenous injection of cyanide. SFMS proved to be an effective antidote for two times the LD90 when administered up to sixty seconds after the cessation of respiration.

Animals↗

In vitro cyanide release of four prussian blue salts used for the treatment of cesium contaminated persons.

Prussian blue salts are used in clinical practice as an antidote for the treatment of humans contaminated with radioactive cesium. A decomposition product of these Prussian blue salts may be the highly toxic cyanide. A method to simulate gastrointestinal cyanide-release was applied to four different Prussian blue salts: K3Fe[Fe(CN)6], Fe4[Fe(CN)6]3, NH4Fe[Fe(CN)6] (pur. and unpur.). Cyanide-release was higher in artificial gastric juice than in water and artificial intestinal juice. Under all conditions cyanide-release from Fe4[Fe(CN)6]3 was the lowest. Since Fe4[Fe(CN)6]3 also binds more cesium, it appears to be the most suitable Prussian blue salt for use as an antidote after radiocesium contamination in humans.

Antidotes↗

Histomorphometric studies on the effect of cyanide consumption of the developing cerebellum of wistar rat (Rattus Novergicus).

OBJECTIVE: To investigate the microscopic effect of maternal cyanide consumption on the developing cerebellum of Wistar rats. MATERIALS AND METHODS: Twenty pregnant female rats weighing between 160 g and 180 g were used in this study. The rats were separated into two groups comprising ten control and ten experimental animals. The control animals were fed a standard diet of mice cubes, while the experimental animals were fed 500 ppm potassium cyanide, mixed with the standard diet. The diets were fed to the animals and their litters in separate cages and water provided ad libitum during pre and postnatal life. After birth, the offspring (five per group) of days 1,9,14,21,28 and 50 were weighed and killed by cervical dislocation. The cerebellar tissues were processed and microscopic parameters studied. RESULTS: A thicker external granular layer (EGL) was seen in the control group on day 1(39+/-9.2microm) compared with the experimental group (29+/-5.8microm) and on day 9(83+/-7.1microm) compared with the experimental group (78+/-13microm). However, these were not significantly different statistically. A thicker and persistent EGL was observed in the experimental group on days 14 and 21. A significant (P<0.05) reduction in the thickness of molecular layer (ML) was observed on days 28 and 50 in the experimental group. The density and size of the Purkinje cells were the same in both the control and experimental groups (P>0.05). CONCLUSION: Maternal consumption of 500 ppm cyanide in rats does not significantly affect light microscopic prenatal cerebellar development, but causes mild changes in the post-natal life. Maternal cyanide consumption causes delayed maturation of the cerebellum, as evidenced by the thicker EGL, and reduction in the ML in the experimental group which become noticeable only at about 28th day of postnatal life.

Animals↗

Cyanide poisoning, 2 cases report and treatment review.

Two patients, a 4-year-old girl and her brother 1 1/2 year-old, with cyanide poisoning are reported. They vomited and became comatose 9 hours after ingestion of boiled cassava. At a community hospital, they were intubated and given ventilatory support. The girl was transferred to Ramathibodi Intensive Care Unit. At 19 hours after ingestion, sodium nitrite and sodium thiosulfate were given as well as other supportive treatment. She recovered with normal breathing on the next day. The boy was referred to Ramathibodi 4 hours later. On arrival, he appeared normal except for the bitter almond breathe. Only supportive treatment was given. Their blood cyanide levels on arrival were 0.56 and 0.32 microgram/ml (normal value < 0.3 microgram/ml) respectively confirming the diagnosis of cyanide poisoning. Other abnormal laboratory findings included metabolic acidosis and lactic acidemia. The pathogenesis and management of cyanide poisoning are reviewed.

Child, Preschool↗