Cyanide poisoning is expected to be antagonized by the administration of oxygen, when it is administered in combination with the conventional cyanide antidote, sodium,thiosulfate. However, the antidotal efficacy and its exact mechanism of oxygen in cyanide poisoning is still a controversial one. To test the effect of oxygen on the antidotal action of thiosulfate ,in cyanide poisoning, author designed this study on the dose-mortality patterns for potassium cyanide in mice. Potency ratios derived from LDso values were compared in groups of mice treated with sodium thiosulfate alone and sodium thiosulfate with oxygen. These results indicated that oxygen enhances the anti-dotal effect of sodium thiosulfate, effectively. This fact demonstrates that oxygen is of importance in the treatment of cyanide poisoning.
Animals ; Mice ; Oxygen* ; Poisoning* ; Potassium Cyanide ; Sodium

The records of 255 cyanide poisoning deaths obtained from National Forensic Service (NFS) headquarters, located in Seoul of Korea, from 2005 to 2010 were retrospectively reviewed. The mean age was 41.88 +/- 13.09 and range was 6~80 years (unknown in seven cases). The number of deaths of males and females were 200 and 53, respectively (unknown in two cases). The largest number of cases occurred in people aged 40-49 years (81 cases, 31.8%), followed by the age groups 30~39 years (51 cases, 20%), 50~59 years (44 cases, 17.2%) and 20~29 years (43 cases, 16.9%). The total number of deaths among other age groups (below 10, 10~19, 60~69, 70~79, over 80 years and unknown) were 36, representing only 14.1%. Of all cyanide poisoning deaths, 97.3% were due to suicide, and 14.5% of the total number who died received medical treatment. The most frequent site for ingestion was the person's own residence (120 cases, 47.1%) and the route of administration was mainly oral (252, 98.8%). From the total of 255 cyanide poisoning cases, white powders were submitted for analysis in 92 cases. Potassium cyanide and sodium cyanide occupied 51 and 41 cases, respectively. This study showed that poisoning deaths due to cyanide are one of the continuously reported public health problems in Korea. Enforcement of regulations and safety education to prevent cyanide poisoning should be carried out by the government.
Aged ; Eating ; Female ; Humans ; Korea ; Male ; Potassium Cyanide ; Powders ; Public Health ; Retrospective Studies ; Social Control, Formal ; Sodium Cyanide ; Suicide

Eating the meat of pheasants which was killed by potassium cyanide, a 27 year old man developed several symptoms of minor intoxication. A few days later, the patient became mute, apathy, somnelent and indifferent but without any parkinsonia features or dementia. On CT brain scan, bilateral symmetrical and non-enhancing focal low densities are noticed in basal ganglia, similar to the carbon monoxide intoxication.
Adult ; Apathy ; Basal Ganglia ; Brain* ; Carbon Monoxide ; Dementia ; Eating ; Humans ; Meat ; Potassium Cyanide

BACKGROUND AND OBJECTIVES: Recent studies have shown that many kinds of K+ channels, including the muscarinic K+ channel (KACh), are activated in the ischemic heart. It is known that these channels can be modulated by phosphorylation. However, little is known about the function of the KACh in ischemic hearts. In this study, we examined whether the KACh channel is mediated by protein kinase C (PKC) activation in rat atrial myocytes under ischemic conditions. MATERIALS AND METHODS: Single atrial cells of adult rat heart were prepared by collagenase digestion. Channel activity of KACh was recorded by cell-attached configuration from single atrial cells under ischemic conditions, using a patch clamp technique. To simulate ischemia, adenosine or potassium cyanide (KCN) was applied to atrial myocytes, and Western blot was performed to specify PKC isoforms. RESULTS: Adenosine and KCN markedly increased KACh channel activity. The responses to adenosine and KCN were increased 3-fold at mean open time from that observed with control. Channel activity of KACh was blocked by pretreatment with PKC antagonists such as sphingosine, Go 6976, and rottlerin. PKC alpha and PKC betaI isoform levels were increased in the membrane fraction of ischemic heart, indicating that ischemic stress might trigger translocation of cytosolic PKC to the cell membrane. CONCLUSION: These results show that KACh channels are modulated by PKC activation under ischemic conditions induced by adenosine or KCN. Therefore, the channels can protect the heart from ischemic stress by increasing channel activity.
Adenosine ; Adult ; Animals ; Blotting, Western ; Cell Membrane ; Collagenases ; Cytosol ; Digestion ; Heart ; Humans ; Ischemia ; Membranes ; Muscle Cells* ; Phosphorylation ; Potassium Cyanide ; Protein Isoforms ; Protein Kinase C* ; Protein Kinases* ; Rats* ; Sphingosine

BACKGROUND AND OBJECTIVES: The overall purpose of this study was to investigate the role of cytochrome C oxidase (CcO) in preventing ischemia reperfusion-induced cardiac injury through gaseous signaling molecule pathways. MATERIALS AND METHODS: We used CcO inhibitor, potassium cyanide (KCN) to mimic the pre-treatment of gaseous signaling molecules in a global ischemia/reperfusion (IR) injury model in rats. Intracellular reactive oxygen species (ROS) was determined by measuring mitochondrial H2O2 and mitochondrial complex activity. RESULTS: KCN pre-treatment led to decreased infarction area after IR injury and improved cardiac function. KCN pre-treated group challenged with IR injury was associated with reduced ROS production through inhibition of activity and not downregulation of CcO expression. In addition, KCN pre-treatment was associated with enhanced expression and activity of mitochondrial antioxidase, suggesting the role of CcO in regulating IR injury through oxidative stress. CONCLUSION: KCN pre-treatment reduced the severity of IR injury. The potential mechanism could be increased endogenous anti-oxidase activity and consequently, the enhanced clearance of ROS.
Animals ; Cytochromes c* ; Cytochromes* ; Down-Regulation ; Electron Transport Complex IV* ; Infarction ; Ischemia* ; Mitochondria ; Myocardial Infarction ; Oxidative Stress ; Potassium Cyanide ; Rats ; Reactive Oxygen Species ; Reperfusion Injury*

OBJECTIVETo investigate the effects of pre-treatment of alpha-ketoglutarate (alpha-KG) on cyanide-induced lethality and changes in various physiological parameters in rodents.

METHODSThe LD50 of potassium cyanide (KCN) given orally (po), intraperitoneally (ip), subcutaneously (sc) or intravenously (iv) was determined in male mice, in the presence or absence alpha-KG given po, ip or iv. alpha-KG was administered 10, 20 or 40 min prior to KCN at 0.50, 1.0 or 2.0 g/kg by po or ip route, and at 0.10, 0.20 or 0.40 g/kg by iv route. Protection index (PI) was calculated as the ratio of LD50 of KCN in the presence of alpha-KG (protected animals) and LD50 of KCN in the absence of alpha-KG (unprotected animals). In a separate experiment, several physiological variables viz. mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), neuromuscular transmission (NMT) and rectal temperature (RT) were measured in anesthetized female rats pre-treated (-10 min) with po (2.0 g/kg) or iv (0.125 g/kg) alpha-KG and then administered sub-lethal (0.75 LD50) or lethal (2.0, 4.0 or 8.0 LD50) doses of KCN (po).

RESULTSPI of 4.52, 6.40 and 7.60 at -10 min, 3.20, 5.40 and 6.40 at -20 min, and 1.40, 3.20 and 5.40 at -40 min of po administration with a-KG was observed for 0.50, 1.0 and 2.0 g/kg doses, respectively, against KCN given by po route. When KCN was given ip, a PI of 3.38, 4.79 and 5.70 was observed for 0.50, 1.0 and 2.0 g/kg alpha-KG given ip (-10 min), respectively. A lower PI of 3.37, 2.83 and 2.38 was observed when KCN given sc was challenged by 2.0 g/kg alpha-KG given ip at -10, -20 or -40 min, respectively. Similarly, a PI of 3.37, 2.83 and 2.0 was noted when KCN given sc was antagonized by 2.0 g/kg alpha-KG given po at -10, -20 or -40 min, respectively. No appreciable protection was observed when lower doses of alpha-KG (ip or po) challenged KCN given by sc route. Pre-treatment of iv or po administration of alpha-KG did not afford any protection against KCN given po or iv route. Oral treatment of 0.75 LD50 KCN caused significant decrease in MAP and HR after 15 min, RR after 30 min and NMT after 60 min. There was no effect on RT. No reduction in MAP, HR, RR and RT was observed when rats received 2.0 or 4.0 LD50 KCN after pre-treatment of alpha-KG (po; 2.0 g/kg). However, no protection was observed on NMT. Protective efficacy of alpha-KG was not observed on MAP, HR, RR, and NMT decreased by 8.0 LD50 KCN. Decrease in MAP and NMT caused by 2.0 LD50 KCN (po) was resolved by iv administration of alpha-KG.

CONCLUSIONSCyanide antagonism by alpha-KG is best exhibited when both alpha-KG and KCN are given by po route. The protective effect of a-KG on cyanide-induced changes in several physiological parameters also indicates a promising role of alpha-KG as an alternative cyanide antidote.

Administration, Oral ; Animals ; Antidotes ; administration & dosage ; Dose-Response Relationship, Drug ; Female ; Injections, Intraperitoneal ; Injections, Intravenous ; Injections, Subcutaneous ; Ketoglutaric Acids ; administration & dosage ; Lethal Dose 50 ; Male ; Mice ; Potassium Cyanide ; poisoning ; Rats ; Rats, Wistar

This study was undertaken to elucidate the underlying mechanisms of ATP depletion-induced membrane transport dysfunction and cell death in renal proximal tubular cells. ATP depletion was induced by incubating cells with 2.5 mM potassium cyanide (KCN)/0.1 mM iodoacetic acid (IAA), and membrane transport function and cell viability were evaluated by measuring Na+-dependent phosphate uptake and trypan blue exclusion, respectively. ATP depletion resulted in a decrease in Na+-dependent phosphate uptake and cell viability in a time-dependent manner. ATP depletion inhibited Na+-dependent phosphate uptake in cells, when treated with 2 mM ouabain, a Na+ pump-specific inhibitor, suggesting that ATP depletion impairs membrane transport functional integrity. Alterations in Na+-dependent phosphate uptake and cell viability induced by ATP depletion were prevented by the hydrogen peroxide scavenger such as catalase and the hydroxyl radical scavengers (dimethylthiourea and thiourea), and amino acids (glycine and alanine). ATP depletion caused arachidonic acid release and increased mRNA levels of cytosolic phospholipase A2 (cPLA2). The ATP depletion-dependent arachidonic acid release was inhibited by cPLA2 specific inhibitor AACOCF3. ATP depletion-induced alterations in Na+-dependent phosphate uptake and cell viability were prevented by AACOCF3. Inhibition of Na+-dependent phosphate uptake by ATP depletion was prevented by antipain and leupetin, serine/cysteine protease inhibitors, whereas ATP depletion-induced cell death was not altered by these agents. These results indicate that ATP depletion-induced alterations in membrane transport function and cell viability are due to reactive oxygen species generation and cPLA2 activation in renal proximal tubular cells. In addition, the present data suggest that serine/cysteine proteases play an important role in membrane transport dysfunction, but not cell death, induced by ATP depletion.
Adenosine Triphosphate ; Amino Acids ; Antipain ; Arachidonic Acid ; Arachidonic Acids ; Catalase ; Cell Death ; Cell Survival ; Cytosol ; Diminazene ; Hydrogen Peroxide ; Hydroxyl Radical ; Iodoacetic Acid ; Membranes ; Ouabain ; Peptide Hydrolases ; Phospholipases A2 ; Potassium Cyanide ; Protease Inhibitors ; Reactive Oxygen Species ; RNA, Messenger ; Trypan Blue

OBJECTIVETo investigate the biochemical changes in rat brain and liver following acute exposure to a lethal dose of cyanide, and its response to treatment of alpha-ketoglutarate (alpha-KG) in the absence or presence of sodium thiosulfate (STS).

METHODSFemale rats were administered 2.0 LD50 potassium cyanide (KCN; oral) in the absence or presence of pre-treatment (-10 min), simultaneous treatment (0 min) or post-treatment (+2-3 min) of alpha-KG (2.0 g/kg, oral) and/or STS (1.0 g/kg, intraperitoneal, -15 min, 0 min or + 2-3 min). At the time of onset of signs and symptoms of KCN toxicity (2-4 min) and at the time of death (5-15 min), various parameters particularly akin to oxidative stress viz. cytochrome oxidase (CYTOX), superoxide dismutase (SOD), glutathione peroxidase (GPx), reduced glutathione (GSH) and oxidized glutathione (GSSG) in brain, and CYTOX, sorbitol dehydrogenase (SDH), alkaline phosphatase (ALP), GSH and GSSG in liver homogenate were measured.

RESULTSAt both time intervals brain CYTOX, SOD, GPx, and GSH significantly reduced (percent inhibition compared to control) to 24%, 56%, 77%, and 65%, and 44%, 46%, 78%, and 57%, respectively. At the corresponding time points liver CYTOX and GSH reduced to 74% and 63%, and 44% and 68%, respectively. The levels of GSSG in the brain and liver, and hepatic ALP and SDH were unchanged. Pre-treatment and simultaneous treatment of a-KG alone or with STS conferred significant protection on above variables. Post-treatment was effective in restoring the changes in liver but failed to normalize the changes in the brain.

CONCLUSIONSOral treatment with alpha-KG alone or in combination with STS has protective effects on cyanide-induced biochemical alterations in rat brain and liver.

Animals ; Antidotes ; pharmacology ; Brain ; drug effects ; metabolism ; Electron Transport Complex IV ; metabolism ; Female ; Glutathione Peroxidase ; metabolism ; Glutathione Reductase ; metabolism ; Ketoglutaric Acids ; pharmacology ; Liver ; drug effects ; metabolism ; Oxidative Stress ; Poisoning ; prevention & control ; Potassium Cyanide ; poisoning ; Rats ; Rats, Wistar ; Superoxide Dismutase ; metabolism ; Thiosulfates ; pharmacology